"annotation_level_1" "annotation_detailed" "description" "marker_genes" "related_refs" "umap_png" "related_cell_ontology"
"PDC" "PDC" "PDC" "pDCs were previously identified by the standard protein marker CD123 (IL3RA). This cluster had higher expression of IRF8, IL3RA and LILRA4 (Villani et al., 2017)" "IRF8,IL3RA,LILRA4" "Villani2017|10.1126/science.aah4573" "pdc_umap.png" NA
"IFN1+ PDC" "PDC" "IFN1+ PDC" "The second pDC subpopulation was identified by standard protein marker CD123 and as IFN-producing cells. This cluster had higher expression of IRF8, IL3RA, LILRA4 and IFI44, IFI6 (Park et al., 2020; Villani et al., 2017)." "IRF8,IL3RA,LILRA5,IFI44,IFI6" "Park2020|10.1126/science.aay3224;Villani2017|10.1126/science.aah4573" "pdc_umap.png" NA
"preB" "preB" "preB" "Precursor B cells were identified by the expression of CD79B, CD19, PAX5, RAG1/2 (Strauchen et al., 2003)." "CD79B,CD19,PAX5,RAG1,RAG2" "Strauchen2003|10.1177/106689690301100105" "pdc_umap.png" NA
"preT" "preT" "preT" "Precursor T cells in tonsils expressed: CD3G, CD8A, RAG1, DNTT, CD1A, CD1B, CD1C, CD1E (McClory et al., 2012)." "CD3G,CD8A,RAG1,DNTT,CD1A,CD1B,CD1C,CD1E" "McClory2012|10.1172/JCI46125" "pdc_umap.png" NA
"Naive" "CD4_T" "Naive" "Naïve cell is a CD4 T cell that recently migrates from the thymus towards lymph nodes. Naïve CD4 T cells expressed lymph node homing genes such as CCR7 and naïve-associated genes: SELL, LEF1, BACH2 and NOSIP. Also, they were negative for PRDM1 and BCL6 and were CD62L+ and CD45RA+ (Cano-Gamez et al., 2020)." "SELL,LEF1,BACH2,NOSIP" "Cano-Gamez2020|10.1038/s41467-020-15543-y" "cd4_t_umap.png" NA
"CM Pre-non-Tfh" "CD4_T" "CM Pre-non-Tfh" "After antigen encounter T cells acquire memory and effector functions maintaining the lymph node homing. CM showed an upregulation of IL7R compared to naïve T cells, and higher expression of PRDM1, PASK, ANXA1 and S100A4. They had an intermediate expression of CCR7 and higher expression of CD28 confirming their migratory capacity to secondary lymph nodes and their memory profile based on their effector function. This cluster was CD45RO+, CD28+ and CD29+(Cano-Gamez et al., 2020; Nicolet et al., 2021)." "CCR7,IL7R,ANXA1,ITGB1,S100A4" "Cano-Gamez2020|10.1038/s41467-020-15543-y;Nicolet2021|10.4049/jimmunol.2100138" "cd4_t_umap.png" NA
"CM Pre-Tfh" "CD4_T" "CM Pre-Tfh" "Early Tfh cell differentiation is regulated by IL-6 and ICOS. This cluster had a similar CM profile, but differential expression of follicular precursors: TCF7, IL6ST and CXCR5, and up-regulation of follicular genes such as ICOS, PDCD1 and TIGIT (Qi, 2016; Sallusto et al., 2004)" "CCR7,IL7R,IL6ST,ANK3,ZBTB16" "Qi2016|10.1038/nri.2016.94;Sallusto2004|10.1146/annurev.immunol.22.012703.104702" "cd4_t_umap.png" NA
"Tfh T:B border" "CD4_T" "Tfh T:B border" "After antigen recognition, CD4 T cells migrate toward the border of the follicle activating B cells. This cluster showed a downregulation on the expression of CCR7 and up-regulation of BCL6, TOX, CXCR5 and BTLA. The expression of ICOS and CD40LG confirmed the interaction with B cells at the border of the follicle (Crotty, 2019)." "TOX,PTPN13,SLC9A9,IL6ST,ICOS,TIGIT" "Crotty2019|10.1016/j.immuni.2019.04.011" "cd4_t_umap.png" NA
"Tfh LZ GC" "CD4_T" "Tfh LZ GC" "Tfh cells provide IL-21 and CD40 signals required for B cell proliferation and differentiation toward both GC and extrafollicular fates. This cluster expressed IL21 and CD40LG. Also, the initial up-regulation of follicular markers as PDCD1. ATAC-seq analysis confirms the activity of BCL6 in this cluster as a follicular T cell subpopulation (Crotty, 2014)." "PASK,ICOS,TIGIT,IL21,IFITM1" "Crotty2014|10.1016/j.immuni.2014.10.004" "cd4_t_umap.png" NA
"GC Tfh SAP" "CD4_T" "GC Tfh SAP" "Terminally differentiated Tfh cells in GC acquired functions depending on the expression of certain markers. This cluster expressed SH2D1A (SAP, top marker) and specific genes and transcription factors associated with GC function: CXCL13, PDCD1 and POU2AF1. SAP was demonstrated to be essential in CD4 T cells for GC responses and the generation of memory B cells and long-lived plasma cells (Crotty, 2011; Booth et al, 2011)" "SH2D1A,ICOS,TIGIT,PCDC1,TOX2,ID3,CXCL13" "Crotty2011|10.1146/annurev-immunol-031210-101400;Booth2011|10.1182/blood-2010-06-284935" "cd4_t_umap.png" NA
"GC Tfh OX40" "CD4_T" "GC Tfh OX40" "OX40 expression (TNFRSF4) on Tfh cells play a role in the maturation and Ig secretion of B cells and plasma cells during GC reaction (Fu et al, 2021). This cluster expressed higher levels of TNFRSF4, CD200, IL21 and IL4 canonical molecules of GC Tfh. IL-21, and IL-4 are major ‘‘help’’ molecules produced by GC Tfh cells to keep GC B cells alive and induce their proliferation (Crotty, 2011). CXCL13, IL-21 and IL- 4 are also potent inducers of IgG1 class switch recombination for human B cells (Choi and Crotty, 2021)." "PDCD1,ICOS,TIGIT,CD200,EGR2,IL21,TNFRSF4,BATF" "Fu2021|10.3389/fimmu.2021.670637;Crotty2011|10.1146/annurev-immunol-031210-101400;Choi2021|10.1016/j.it.2021.02.002" "cd4_t_umap.png" NA
"Tfh Mem" "CD4_T" "Tfh Mem" "Upon leaving a GC, the Tfh cell acquires a less activated, less polarized Tfh phenotype and can upregulate KLRB1 and develop into resting memory Tfh cells. This cluster had the expression of follicular markers PDCD1, MAF, and higher expression of memory markers such as KLRB1, ITGB1 and CD28 (Crotty, 2014)" "PDCD1,CD128,MAF,IKZF3,TNFRSF1B" "Crotty2014|10.1016/j.immuni.2014.10.004" "cd4_t_umap.png" NA
"T Trans-Mem" "CD4_T" "T Trans-Mem" "Transitional memory T cells appear to be more differentiated than TCM cells but not as fully differentiated as TEM cells in terms of phenotype. This cluster had higher levels of IL7R, CD28, CCR6, RORA and lower KLRB1. This cluster was CD62L-, CD45RO+ and CD28+ (Mahnke et al., 2013)." "IL7R,CD28,CCR6,RORA,KLRB1" "Mahnke2013|10.1002/eji.201343751" "cd4_t_umap.png" NA
"T-Eff-Mem" "CD4_T" "T-Eff-Mem" "Following antigen clearance, effector cells die while a small pool of T cells ultimately develops into long-lived effector memory T cells. This cluster was positive for KLRB1, HECW2, and EGLN3. The phenotype of this cluster included CD45R0+, CD161+ and CD62L- (Cano-Gamez et al., 2020; Mahnke et al., 2013)." "KLRB1,HECW2,EGLN3" "Cano-Gamez2020|10.1038/s41467-020-15543-y;Mahnke2013|10.1002/eji.201343751" "cd4_t_umap.png" NA
"T-helper" "CD4_T" "T-helper" "T helper cells play a critical role in defending infections by coordinating immune responses. CD4 T cells execute their functions mainly in peripheral tissues and various lymphoid organs. CD4 T cells receive signals from the environment and differentiate into specific subsets of T helper cells to efficiently recognize a broad range of antigens (Zhu and Zhu, 2020)." "IL17A,CCL4,IL26,CCL20,CXCR6" "Zhu2020|10.3390/ijms21218011" "cd4_t_umap.png" NA
"Th1" "CD4_T" "Th1" "Th1 cells induce responses against intracellular pathogens by activating macrophages. This cluster expressed CXCR3, TBX21, GZMK and CCR5, main markers of Th1 cells (Krueger et al., 2021)." "CXCR3,TBX21,GZMK,CCR5" "Krueger2021|10.1016/j.immuni.2021.03.006" "cd4_t_umap.png" NA
"Th2" "CD4_T" "Th2" "Th2 cells are involved in type 2 responses to fight infections by parasites such as helminths, as well as the recruitment of eosinophils, basophils, and mast cells to the sites of infections. This cluster had higher expression of CCR4, GATA3, IL17RB and IL4IL (Cano-Gamez et al., 2020; Stark et al., 2019)." "CCR4,GATA3,IL17RB,IL4IL" "Cano-Gamez2020|10.1038/s41467-020-15543-y;Stark2019|10.3389/fimmu.2019.02318" "cd4_t_umap.png" NA
"Th17" "CD4_T" "Th17" "Th17 cells mediate responses for the clearance of extracellular bacteria and fungi by orchestrating sustained neutrophil recruitment. This cluster had higher expression of CCR6, RORC, IL17A and IL17F (Ma et al., 2016)." "CCR6,RORC,IL17A,IL17F" "Ma2016|10.1084/jem.20151467" "cd4_t_umap.png" NA
"Th17/Th1" "CD4_T" "Th17/Th1" "Th17 cells can convert to Th1 cells based on the cytokine environment. This cluster had expressions of IFNG, IL26 and IL17A (Damsker et al., 2010)." "IFNG,IL26,IL17A" "Damsker2010|10.1111/j.1749-6632.2009.05133.x" "cd4_t_umap.png" NA
"Th22" "CD4_T" "Th22" "Th22 cells are players in adaptive immune responses and are identified by the production of IL-22. This cluster had higher levels of IL22, IL10 and TNF (Jia and Wu, 2014)." "IL22,IL10,TNF" "Jia2014|10.1007/978-94-017-9487-9_8" "cd4_t_umap.png" NA
"Eff-Tregs" "CD4_T" "Eff-Tregs" "Effector T regulatory cells play an important role in maintaining the homeostasis in tissues and control immune responses. This cluster is the classical Treg subpopulation that expresses IL2RA, CTLA4, IL1R1, IL1R2 and IL10 and specific transcription factors FOXP3, MAF, IKZF1 and IKZF3, and it is CD25+ and CD28+ (Du et al., 2021)." "IL2RA,CTLA4,IL1R1,IL1R2,IL10" "Du2021|10.1007/978-981-15-6407-9_1" "cd4_t_umap.png" NA
"Eff-Tregs-IL32" "CD4_T" "Eff-Tregs-IL32" "This cluster had a similar profile of Eff-Tregs, it showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like IL32. This cluster had as top genes: IL32, FOXP3, CTLA4, IL2RA and IKZF2 (Galván-Peña et al., 2021)." "IL32,FOXP3,CTLA4,IL2RA,IKZF2" "Galván-Peña2021|10.1073/pnas.2111315118" "cd4_t_umap.png" NA
"Tfr" "CD4_T" "Tfr" "T-follicular regulatory cells in the tonsils are CD25-. These cells down-regulate effector Treg markers (IL2RA, FOXP3, CTLA4). This cluster expressed high levels of FCRL3, CLNK, LEF1, TCF7, RBMS3, SESN3, and PDE3B. The top marker FCRL3 can bind secretory IgA to suppress the Tfr inhibitory function. TCF7 and LEF1 are essential for Tfr development in mice (Wing et al., 2017; Agarwal et al., 2020 ; Yang et al., 2019)." "FCRL3,CLNK,LEF1,TCF7,RBMS3,SESN3,PDE3B" "Wing2017|10.1073/pnas.1705551114;Agarwal2020|10.1016/j.celrep.2019.12.099;Yang2019|10.1016/j.celrep.2019.05.061" "cd4_t_umap.png" NA
"Cycling T" "CD4_T" "Cycling T" "This cluster is a T cell cluster (CD3+) that had a higher score of cell cycle and had higher expression of cell cycle genes: STMN1, HIST1H4C, TUBA1B, HMGB2, MKI67, TOP2A and TUBB. As we observed that the proliferative signature was a major driver of variance in scRNA-seq data, which caused (1) cells from different lineages to cluster together and (2) hindered biological heterogeneity in the other cluster. Thus we show this population in Figure 1B, but exclude it from downstream analysis. A cluster of cycling T was also observed in (King et al., 2021)." "CD3D,STMN1,HIST1H4C,TUBA1B,HMGB2,MKI67,TOP2A,TUBB" "King2021|10.1126/sciimmunol.abe6291" "cd4_t_umap.png" NA
"Naive CD8 T" "Cytotoxic" "Naive CD8 T" "Naive cell is a CD8 T cell that recently migrates from the thymus towards lymph nodes. This cluster expressed BACH2, LEF1, NOSIP and CCR7. Also, this cluster was CD45RA+ (Mahnke et al. 2013)." "BACH2,LEF1,NOSIP,CCR7" "Mahnke2013|10.1002/eji.201343751" "cytotoxic_umap.png" NA
"SCM CD8 T" "Cytotoxic" "SCM CD8 T" "Stem-cell memory T cells self-renew and generate long-lived central memory T cells and short-lived effector memory T cells. Differential expression analysis reveals these genes as the main markers: FAM117B, TCF7, TSHZ2 and PLAC8. This population was CD95+ and CXCR3+ (Galletti et al., 2020; Gattinoni et al. 2011)." "FAM117B,TCF7,TSHZ2,PLAC8" "Galletti2020|10.1038/s41590-020-0791-5;Gattinoni2011|10.1038/nm.2446" "cytotoxic_umap.png" NA
"CM CD8 T" "Cytotoxic" "CM CD8 T" "CM CD8 T cells acquire memory (marked by IL7R+) while maintaining lymph node homing capacity (CCR7+). CM expressed higher levels of IL7R compared to naïve T cells, and higher expression of ANXA1 and S100A4. They had an intermediate expression of CCR7 and a higher expression of CD28. This cluster was CD45RO+, and CD28+ (Mahnke et al. 2013)." "IL7R,ANXA1,S100A4,CCR7,CD28" "Mahnke2013|10.1002/eji.201343751" "cytotoxic_umap.png" NA
"RM CD8 T" "Cytotoxic" "RM CD8 T" "Resident memory T cells (TRM) are essential for immune defense against pathogens and malignancies. The unique identity of TRM cells in tissues is defined by a combination of decreased expression of proteins that facilitate their exit from tissues and increased expression of proteins that enhance their ability to stay in tissues (e.g. CD103 and CD49a). A pool of TRM-poised cells generate RM CD8 T cells within the tonsil compartment. The main gen markers of this cluster are: CD69, EOMES, ZEB2, ITGA1 and TOX, and CD69+ (Kok et al., 2022)." "CD69,EOMES,ZEB2,ITGA1,TOX" "Kok2022|10.1038/s41577-021-00590-3" "cytotoxic_umap.png" NA
"RM CD8 activated T" "Cytotoxic" "RM CD8 activated T" "This cluster had a similar profile of RM T cells but it had higher expression of GZMH, CCL5, GZMA, GZMK, CXCR6, HLA-DRB1, HLA-DPA1 and CD38. These markers showed an activated profile of these RM CD8 T cells. Also, It was positive for CD103 and CD54. Intriguingly, this cluster had a lower expression of CD69 compared with the other RM subset (Kok et al., 2022; Walsh et al., 2019)." "ITGA1,GZMH,CCL5,GZMA,GZMK,CXCR6,HLA-DRB1,HLA-DPA1,CD38" "Kok2022|10.1038/s41577-021-00590-3;Walsh2019|10.4049/jimmunol.1900052" "cytotoxic_umap.png" NA
"EM CD8 T" "Cytotoxic" "EM CD8 T" "This cluster is CCR7- and expresses high levels of CX3CR1, TBX21 (Gerlach et al., 2016), and multiple cytotoxicity genes, including GZMB, GZMH, GZMA, PRF1, and GNLY. TBX21 and EOMES motifs are highly active in this cluster (scATAC-seq data)." "CX3CR1,TBX21,GZMB,GZMH,GZMA,PRF1,GNLY" "Gerlach2016|10.1016/j.immuni.2016.10.018" "cytotoxic_umap.png" NA
"CD8 Tf" "Cytotoxic" "CD8 Tf" "CD8+ T cells located within the lymphoid follicle are follicular CD8+ T cells that play an important role in viral and tumor control, as well as to modulate humoral and T follicular helper cell responses. This cluster expressed high levels of CD200, CXCL13, ICOS, PDCD1 and IFNG, and it was CXCR5+, PD-1+ and ICOS+ (Perdomo-Celis et al., 2017)." "CXCL13,PDCD1,ICOS,CD200" "Perdomo-Celis2017|10.3389/fimmu.2017.01241" "cytotoxic_umap.png" NA
"DC recruiters CD8 T" "Cytotoxic" "DC recruiters CD8 T" "CD8+ T cells can orchestrate the local recruitment of tonsil-resident XCR1+ DCs via secretion of the XCL1 chemokine. Functionally, this CD8+ T cell-mediated reorganization of the local DC network allows for the interaction and cooperation of pDCs and XCR1+ DCs. This cluster had as top markers CCL5, XCL2, XCL1 and CCL4. These markers confirmed their role in the recruitment of DCs (Brewitz et al., 2017)." "CD160,CCL5,XCL2,XCL1,CCL4" "Brewitz2017|10.1016/j.immuni.2017.01.003" "cytotoxic_umap.png" NA
"IFN+ CD8 T" "Cytotoxic" "IFN+ CD8 T" "This cluster had an expression of genes related with IFNg responses. The up-regulated genes were HLA-DRB1, IFIT3, IFIT5 and IFITM2." "HLA-DRB1,IFIT3,IFIT5,IFITM2" "Li2022|10.3389/fimmu.2022.1056144;Szabo2019|10.1038/s41467-019-12464-3" "cytotoxic_umap.png" NA
"non-Vδ2+ γδ T" "Cytotoxic" "non-Vδ2+ γδ T" "γδ T cells are a distinct subgroup of T cells containing T cell receptors (TCR) γ and δ chains. In this cluster we identified a clear signature of gd T cells: KLRD1, KLRC2, TRGC1, TRGC2 and TRDC (Pizzolato et al., 2019)." "KLRD1,KLRC2,TRGC1,TRGC2,TRDC" "Pizzolato2019|10.1073/pnas.1818488116" "cytotoxic_umap.png" NA
"MAIT/Vδ2+ γδ T" "Cytotoxic" "MAIT/Vδ2+ γδ T" "This cluster is a mix of MAIT cells (KLRB1, SLC4A10, ZBTB16, IL23R, IL18R1, CEPBD, CCR6, DPP4) and Vδ2Vγ9+ γδ T cells (TRDV2, TRDC, TRGC1, TRGC2, ZBTB16, KLRB1, IL18R1, DPP4) which share a similar phenotype and transcriptional profile (Provine et al., 2018; Wragg et al., 2020)." "KLRB1,SLC4A10,ZBTB16,IL23R,IL18R1,TRDV2,TRDC,TRGC1" "Provine2018|10.3389/fimmu.2018.00756;Wragg2020|10.1016/j.celrep.2020.107773" "cytotoxic_umap.png" NA
"ZNF683+ CD8 T" "Cytotoxic" "ZNF683+ CD8 T" "This cluster is CD8+, expresses ZNF683 (HOBIT), NCAM1 (CD56), GNLY, GZMB, tissue-resident memory T cell markers (ITGAE, ITGA1), and multiple NK cell receptors, including KLRC2 (NKG2C), KLRC3 (NKG2E), KLRD1 (CD94), and KIR2DL4. A ZNF683+ CD8 T cluster was also reported in the thymus atlas. (Park et al., 2020)" "ZNF683,NCAM1,GNLY,ITGAE,ITGA1,KLRC2,KLRC3" "Park2020|10.1126/science.aay3224" "cytotoxic_umap.png" NA
"CD16-CD56+ NK" "Cytotoxic" "CD16-CD56+ NK" "These cells have an immunoregulatory function, possess a strong ability to react to cytokine stimulation, are mainly found in secondary lymphoid organs, and have limited cytotoxic capacity. They are the precursors of CD16+CD56- NK cells. This cluster expressed KLRF1, NCAM1, SELL, TCF7, GZMK, and XCL1. (Boldt et al., 2014; Pfefferle et al. 2019; Poli et al. 2009)." "KLRF1,NCAM1,SELL,TCF7,GZMK,XCL1" "Boldt2014|10.1002/cyto.b.21162;Pfefferle2019|10.1101/630657;Poli2009|10.1111/j.1365-2567.2008.03027.x" "cytotoxic_umap.png" NA
"CD16-CD56dim NK" "Cytotoxic" "CD16-CD56dim NK" "An intermediate NK cell subtype between precursor (CD16-CD56+) and differentiated NK cells (CD16+CD56-). This cluster expressed KLRF1, XCL1, and XCL2. (Boldt et al., 2014; Pfefferle et al. 2019; Poli et al. 2009)." "KLRF1,XCL1,XCL2" "Boldt2014|10.1002/cyto.b.21162;Pfefferle2019|10.1101/630657;Poli2009|10.1111/j.1365-2567.2008.03027.x" "cytotoxic_umap.png" NA
"CD16+CD56- NK" "Cytotoxic" "CD16+CD56- NK" "Fully differentiated NK cells with high cytotoxic capacity. This cluster had a high expression of KLRF1, FCGR3A, CX3CR1, TBX21, and PRF1 (Boldt et al., 2014; Pfefferle et al. 2019; Poli et al. 2009)" "KLRF1,FCGR3A,CX3CR1,TBX21,PRF1" "Boldt2014|10.1002/cyto.b.21162;Pfefferle2019|10.1101/630657;Poli2009|10.1111/j.1365-2567.2008.03027.x" "cytotoxic_umap.png" NA
"ILC1" "Cytotoxic" "ILC1" "ILC1 are characterized by their capacity to produce IFNγ and they depend on the transcription factor T-bet. Contrary to NK cells, ILC1 express IL7R (CD127) and CD200R; and do not express KLRF1 (NKp80). Accordingly, this cluster expressed high levels of IL7R, CD200R1, CD69 and ANXA1; and did not express KLRF1 (Boldt et al., 2014; Vivier et al., 2018)." "IL7R,CD200R1,CD69,ANXA1" "Boldt2014|10.1002/cyto.b.21162;Vivier2019|10.1016/j.cell.2018.07.017" "cytotoxic_umap.png" NA
"NKp44+ ILC3" "Cytotoxic" "NKp44+ ILC3" "ILC3s depend on RORC for their development and function, and comprise subsets that can be distinguished on the basis of expression of the natural cytotoxicity receptors NKp46 and NKp44. The main cytokine produced by ILC3s is IL-22 and a proportion of ILC3s also produce IL-17. This cluster expressed RORC, IL23R and NCR2 (Nkp44; Boldt et al., 2014; Vivier et al., 2018)." "IL7R,RORC,IL23R,NCR2" "Boldt2014|10.1002/cyto.b.21162;Vivier2019|10.1016/j.cell.2018.07.017" "cytotoxic_umap.png" NA
"NKp44- ILC3" "Cytotoxic" "NKp44- ILC3" "ILC3s depend on RORC for their development and function, and comprise subsets that can be distinguished on the basis of expression of the natural cytotoxicity receptors NKp46 and NKp44. The main cytokine produced by ILC3s is IL-22 and a proportion of ILC3s also produce IL-17. This cluster expressed RORC, IL23R, but not NCR2 (Nkp44; Boldt et al., 2014; Vivier et al., 2018)." "IL7R,RORC,IL23R" "Boldt2014|10.1002/cyto.b.21162;Vivier2019|10.1016/j.cell.2018.07.017" "cytotoxic_umap.png" NA
"DN" "Cytotoxic" "DN" "Double negative T cells express the αβ T cell receptor but do not express CD4, CD8, or natural killer cell markers. This cluster had a profile of inflammatory and activated DN T cells expressing HLA-DRB1, HLA-DPA1, CD38 and GPR183 (Wu et al., 2022b)." "HLA-DRB1,HLA-DPA1,CD38,GPR183" "Wu2022|10.3389/fimmu.2022.816005" "cytotoxic_umap.png" NA
"NBC" "NBC_MBC" "NBC" "This is the main cluster of NBCs, with a clear and homogenous expression of FCER2 (CD23), TCLA1, IGHM and IGHD. This cluster seems to represent standard NBC lacking the expression of genes related to cell activation or commitment towards GC reaction. We would like to clarify that we performed a targeted search for two known NBC subpopulations that are expected to be present in tonsillar tissue, i.e. CD5 Mature NBCs and transitional B cells. However, CD5, a key marker to define these subpopulations, could not be detected by scRNA-seq. We also used alternative gene signatures defined by Seifert et al. (Seifert et al., 2012) but we could not detect any particular subcluster. Therefore, although we cannot rule out that CD5 Mature NBCs and transitional B cells are present in our dataset -probably within the standard NBC cluster-, we could not identify them." "FCER2,TCLA1,IGHM,IGHD" "Seifert2012|10.1084/jem.20120833" "nbc_mbc_umap.png" NA
"NBC early activation" "NBC_MBC" "NBC early activation" "Cells in this cluster show expression of typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. This cluster is transcriptionally very similar to standard NBCs, with the exception of a few genes related to B cell activation, such as CD69 and IL4R (Cibrián and Sánchez-Madrid, 2017; Ferrer et al., 2014). Therefore, these cells seem to represent the first step of NBC activation." "FCER2,TCLA1,IGHM,IGHD,CD69,IL4R" "Cibrián2017|10.1002/eji.201646837;Ferrer2014|10.1111/bjh.12645" "nbc_mbc_umap.png" NA
"NBC INF-activated" "NBC_MBC" "NBC INF-activated" "Cells in this cluster expressed typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. Several genes expressed exclusively by the cells in these clusters are associated with interferon induction, as for example ISG15, the IFIT gene family (i.e. or IFIT1, IFIT2 or IFIT3) family, IFI44, IFI44L and MX1. Thus, this cluster represents NBC cells that have been activated in response to interferon stimulation." "FCER2,TCLA1,IGHM,IGHD,ISG15,IFIT1,IFIT2,IFI44,IFI44L,MX1" NA "nbc_mbc_umap.png" NA
"NBC CD229+" "NBC_MBC" "NBC CD229+" "Cells in this cluster express typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. As compared to the standard NBC cluster, only few genes were differentially expressed. We identified two main markers, related to immune system and B cell biology that were specifically expressed within this cluster, i.e. LY9 (CD229), which has been shown to be highly expressed in marginal zone B cells (Cuenca et al., 2016) and LILRA4 (Cao and Bover, 2010), which actually is more relevant for plasmacytoid dendritic cells. Unfortunately, the lack of literature related to this particular combination of markers precluded us from assigning a biological function to this cluster." "FCER2,TCLA1,IGHM,IGHD,LY9,LILRA4" "Cuenca2016|10.4049/jimmunol.1501266" "nbc_mbc_umap.png" NA
"Early GC-committed NBC" "NBC_MBC" "Early GC-committed NBC" "Cells in this cluster express typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. This cluster is characterized by the expression of very specific genes that seem to correspond to early GC commitment due to the transient MYC upregulation (Dominguez-Sola et al., 2012). For instance, we observed high expression of EGR family (i.e. EGR1, EGR2, EGR3), transcription factors that are rapidly induced upon stimulation of the BCR (Gururajan et al., 2009); genes related to NF-kB pathway (i.e. NFKB1, NFKB2, NFKBIA, NFKBID, RELB; Stevenson et al., 2011); or proinflammatory chemokines i.e. CCL3 and CCL4 (Takahashi et al., 2015). Furthermore, in this cluster we identified high levels of bone-fide activation marker, i.e. CD69 (Cibrián et al., 2017). As this marker was also present at lower levels in the NBC early activation cluster, we hypothesize that these two clusters represent sequential steps of the NBC activation process towards the GC reaction" "FCER2,TCLA1,IGHM,IGHD,EGR1,EGR2,EGR3,NFKB1,NFKB2,NFKBIA,NFKBID,RELB,CCL3,CCL4" "Dominguez-Sola2012|10.1038/ni.2428;Gururajan2009|10.4049/jimmunol.181.7.4590;Stevenson2011|10.1182/blood-2011-06-338855;Takahashi2015|10.1111/bjh.13659;Cibrián2017|10.1002/eji.201646837" "nbc_mbc_umap.png" NA
"GC-committed NBC" "NBC_MBC" "GC-committed NBC" "Cells in this cluster express typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. This cluster seems to follow the Early GC-committed NBCs in the differentiation path between NBC and GCBCs. For instance, one of the main markers of this cluster is CCND2, which is a bona fide downstream target of MYC (a marker for early GC commitment, (Dominguez-Sola et al., 2012). It also maintains the expression of NF-kB pathway related genes. Furthermore, the cells in this cluster express genes associated with signaling pathways related to response to antigens, such as MIR155HG, TRAF1/4, EBI3, and BCL2A1. Finally, we observed upregulation of BATF, a gene known to be involved in the regulation of AID (AICDA) expression and thus antibody diversification in DZ-GCBCs (Ise et al., 2011). Although this cluster lacks any GC-related marker, it seems to represent a cell stage that is already committed to enter the GC reaction." "FCER2,TCLA1,IGHM,IGHD,CCND2,MIR155HG,TRAF1,TRAF4,EBI3,BCL2A1" "Dominguez-Sola2012|10.1038/ni.2428;Ise2011|10.1038/ni.2037" "nbc_mbc_umap.png" NA
"preGC" "NBC_MBC" "preGC" "Cells in this cluster express typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. As compared to the preceding clusters related to NBC activation, within this cluster we could detect the expression of GC-specific genes, such as RGS13 or MEF2B (King et al., 2021). However, these cells still partially maintain the NBC transcriptome and transcriptional programs started in the previous steps of NBC activation process (i.e. GC-committed NBC) such as the BATF expression. Additionally, this cluster still lacks other GC phenotypic genes, such as AICDA or BCL6. Therefore, we conclude that this subcluster may represent the last step of NBC activation before entering into the DZ and starting a proper GC reaction." "FCER2,TCLA1,IGHM,IGHD,RGS13,MEF2B,BATF" "King2021|10.1126/sciimmunol.abe6291" "nbc_mbc_umap.png" NA
"Proliferative NBC" "NBC_MBC" "Proliferative NBC" "Cells in this cluster express typical NBC markers such as FCER2 (CD23), TCLA1, IGHM and IGHD. This cluster is characterized by a proliferation signature, marked by high expression of MKI67, TOP2A, histone genes and genes related with chromosome segregation. Intriguingly, this cluster does not contain any marker related to GC, i.e. lack of expression of RGS13, MEF2B (the two expressed in preGC cluster), AICDA and BCL6. We therefore discarded that these cells were related to the GC-dependent maturation pathway of NBCs. Instead, we hypothesize that this population may correspond to primary focal reaction upon antigen stimulation (Jacob and Kelsoe, 1992), which leads to rapid generation of antibody-producing cells in a GC-independent manner." "FCER2,TCLA1,IGHM,IGHD,MKI67,TOP2A" "Jacob1992|10.1084/jem.176.3.679" "nbc_mbc_umap.png" NA
"Early MBC" "NBC_MBC" "Early MBC" "This cluster of the NBC/MBC level 1 cluster is CD27 positive, and therefore, we annotate it as MBC. However, this cluster does not have many specific markers, with the exception of e.g. low-medium levels of MEF2B, a GC marker. This might suggest that this cluster represents MBCs freshly generated from the GC reaction, and still contains traces of GC markers such as MEF2B (King et al., 2021)." "MS4A1,CD79A,CD79B,CD27,MEF2B" "King2021|10.1126/sciimmunol.abe6291" "nbc_mbc_umap.png" NA
"ncsMBC" "NBC_MBC" "ncsMBC" "This is one of the main clusters of MBCs, with clear expression of known markers such as CD27 and CD267. It is also characterized by high expression of IGHD and IGHM, and therefore, this cluster is classified as non-class switch MBC (ncsMBCs; Akkaya et al., 2020)." "MS4A1,CD79A,CD79B,CD27,TNFRSF13B,IGHD,IGHM" "Akkaya2020|10.1038/s41577-019-0244-2" "nbc_mbc_umap.png" NA
"csMBC" "NBC_MBC" "csMBC" "This is one of the main clusters of MBCs, with clear expression of known markers such as CD27 and CD267. It is also characterized by high expression of IGHA1 and IGHG1, and therefore it is classified as class switch MBC (csMBCs; Akkaya et al., 2020)." "MS4A1,CD79A,CD79B,CD27,TNFRSF13B,IGHA1,IGHG1" "Akkaya2020|10.1038/s41577-019-0244-2" "nbc_mbc_umap.png" NA
"ncsMBC FCRL4/5+" "NBC_MBC" "ncsMBC FCRL4/5+" "This is a subcluster of ncsMBC (positive for CD27, CD267, IGHD and IGHM), characterized by the expression of FCRL4 and FCRL5. This subpopulation is typically found in tonsils but not in peripheral blood or bone marrow. In concordance with the available literature related to FCRL4+ MBCs, this cluster expresses high levels of GSN, SOX5, FGR or HCK, among others (Li et al., 2020)" "MS4A1,CD79A,CD79B,CD27,TNFRSF13B,IGHD,IGHM,FCRL4,FCRL5,GSN,SOX5,FGR,HCK" "Li2020|10.1093/intimm/dxaa053" "nbc_mbc_umap.png" NA
"csMBC FCRL4/5+" "NBC_MBC" "csMBC FCRL4/5+" "This is a subcluster of csMBC (positive for CD27, CD267, IGHA and IGHG), characterized by the expression of FCRL4 and FCRL5. This subpopulation is typically found in tonsils but not in peripheral blood or bone marrow. In concordance with the available literature related to FCRL4+ MBCs, this cluster expresses high levels of GSN, SOX5, FGR or HCK, among others (Li et al., 2020)" "MS4A1,CD79A,CD79B,CD27,TNFRSF13B,IGHA1,IGHG1,FCRL4,FCRL5,GSN,SOX5,FGR,HCK" "Li2020|10.1093/intimm/dxaa053" "nbc_mbc_umap.png" NA
"MBC FCRL5+" "NBC_MBC" "MBC FCRL5+" "This is a low abundant cluster of MBC cells (positive for CD27 and CD267) that present and intermediate transcriptomic signature between csMBC and csMBC FCRL4+/FCRL5+. These cells express only FCRL5 with the absence of FCRL4. This subpopulation has been described as MBC FCRL5-only, which indeed was shown to express many genes at intermediate level between FCRL4/FCRL5 MBCs and MBC (Li et al., 2020)" "MS4A1,CD79A,CD79B,CD27,TNFRSF13B,IGHA1,IGHG1,FCRL5,GSN,SOX5,FGR,HCK" "Li2020|10.1093/intimm/dxaa053" "nbc_mbc_umap.png" NA
"DZ-early S phase" "GCBC" "DZ-early S phase" "Cluster with high expression of CXCR4 (a marker defining DZ GCB cells) and additional expression of DZ markers, such as FOXP1 and MME, and moderate levels of AICDA (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). This cluster displays a clear proliferation signature and high S-phase score. Cells express typical cell cycle genes, such as MCM family, POLA1 or PCNA, which are associated with DNA replication and strand elongation as well as G1/S transition GO terms. This cluster lacks expression of histone genes (i.e. HIST1H4C, HIST1H1B, HIST2H2AH, HIST1H3D), which are related to a more advanced S phase. Therefore, the present cluster most likely represents the early steps of the S phase of the cell cycle (Bar-Joseph et al., 2008)." "CXCR4,MME,FOXP1,AICDA,POLA1,PCNA,MCM5,MCM7,MCM4,MCM6" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"DZ-late S phase" "GCBC" "DZ-late S phase" "Cluster with high expression of CXCR4 (a marker defining DZ GCB cells) and additional expression of DZ markers, such as FOXP1 and MME, and moderate levels of AICDA (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). This cluster displays a clear proliferation signature and high S-phase score. Cells express typical cell cycle genes, such as MCM family, POLA1 or PCNA, which are associated with DNA replication and strand elongation as well as G1/S transition GO terms. This cluster shows upregulation of histone genes (i.e. HIST1H4C, HIST1H1B, HIST2H2AH, HIST1H3D), suggesting that it contains cells associated with the later steps of the S phase. Moreover, the cells within this cluster start expressing the first traces of genes related to more advanced phases of the cell cycle, such as AURKB, TOP2A or MKI67 (Bar-Joseph et al., 2008)." "CXCR4,MME,FOXP1,AICDA,POLA1,PCNA,MCM5,MCM7,MCM4,MCM6,HIST1H4C,HIST1H1B,HIST2H2AH,HIST1H3D" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"DZ-early G2M phase" "GCBC" "DZ-early G2M phase" "Cluster with high expression of CXCR4 (a marker defining DZ GCB cells) and additional expression of DZ markers, such as FOXP1 and MME, as well as high expression of AICDA (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). This cluster has a clear G2M phase score. It is characterized by high expression of genes related to spindle organization, chromosome segregation, mitotic cell cycle and division, i.e. BUB1, TOP2A, centromere proteins family, tubulin genes, AURKA, CDK1 and MKI67. Cells from this cluster start to downregulate the expression of histone genes concomitantly with the upregulation of cyclin B genes and CDC20, indicating full entry into mitosis (Bar-Joseph et al., 2008)." "CXCR4,MME,FOXP1,AICDA,BUB1,TOP2A,AURKA,CDK1,MKI67,TUBB4B,HIST1H4C,HIST1H1B" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"DZ-late G2M phase" "GCBC" "DZ-late G2M phase" "Cluster with high expression of CXCR4 (a marker defining DZ GCB cells) and additional expression of DZ markers, such as FOXP1 and MME, as well as high expression of AICDA (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). This cluster has a clear G2M phase score. It is characterized by high expression of genes related to spindle organization, chromosome segregation, mitotic cell cycle and division, i.e. BUB1, TOP2A, centromere proteins family, tubulin genes, AURKA, CDK1 and MKI67. Cells from this cluster start to downregulate the expression of histone genes concomitantly with the upregulation of cyclin B genes and CDC20, indicating full entry into mitosis (Bar-Joseph et al., 2008)." "CXCR4,MME,FOXP1,AICDA,BUB1,TOP2A,AURKA,CDK1,MKI67,TUBB4B,CCNB2,CDC20" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"DZ-cell cycle exit" "GCBC" "DZ-cell cycle exit" "Cluster with high expression of CXCR4 (a marker defining DZ GCB cells) and additional expression of DZ markers, such as FOXP1 and MME, as well as moderate expression of AICDA (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). Cells from this cluster start to downregulate the expression levels of cell cycle program genes. For instance, they lack CDK1 but still contain lower levels of CCNB1, CDC20, TOP2A and MKI67 as compared to the cells from preceding DZ-G2M phase clusters. The cells still maintain clear expression of other proliferation-related genes such as HMG family genes, STMN1 or BIRC5. This cluster was not associated with any significant upregulation as compared to the preceding cluster (DZ-late G2M phase). Therefore, we defined this cluster as dark zone cells that have started to exit the cell cycle (Bar-Joseph et al., 2008)." "CXCR4,MME,FOXP1,AICDA,CCNB1,CDC20,TOP2A,MKI67,STMN1,BIRC5,HMGB2" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"DZ-non-proliferative" "GCBC" "DZ-non-proliferative" "Cluster with high expression of CXCR4 (a marker defining DZ GCB cells) and additional expression of DZ markers, such as FOXP1 and MME, as well as moderate expression of AICDA (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). Cells from these clusters are clearly non-proliferative, lacking the detectable expression of any cell cycle gene. Therefore, we hypothesize that cells in this cluster, although they maintain the expression of dark zone-related genes, have already finished the cell cycle program and are progressing towards the next maturation stage (Bar-Joseph et al., 2008)." "CXCR4,MME,FOXP1,AICDA" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"DZ-LZ transition" "GCBC" "DZ-LZ transition" "This relatively large non-proliferative cluster is characterized by rather intermediate or low expression of DZ markers, such as CXCR4. The cells start to express some LZ markers such as CD83 or LMO2, but still are missing other LZ-genes such as BCL2A1 or DUSP2 (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). Furthermore, we could not define clear markers specific and unique for this cluster. From the chromatin perspective, this cluster contained intermediate levels of regions differentially accessible between the DZ and the LZ. Therefore, we believe that these cells represent a transitional subpopulation moving from the DZ to the LZ." "CXCR4,CD83,LMO2" "King2021|10.1126/sciimmunol.abe6291" "gcbc_umap.png" NA
"LZ" "GCBC" "LZ" "Cells in this non-proliferative cluster show expression of well-known light zone markers, i.e. CD83, LMO2, and downregulation of DZ genes such as CXCR4 or AICDA. Within this cluster, genes related to CD40 signaling and response to BCR stimulation are starting to be expressed (e.g. BCL2A1, BCL2L1, TRAF1/4 or EBI3). However, the expression levels of these genes were not homogeneous, suggesting the presence of different levels of activation of LZ cells (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018)." "CD83,LMO2,BCL2A1,BCL2L1,TRAF1,TRAF3,EBI3" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4" "gcbc_umap.png" NA
"LZ-DZ re-entry commitment" "GCBC" "LZ-DZ re-entry commitment" "Cluster with high expression of CD83 and low expression of CXCR4, as well as positive for LMO2, which indicate that this cluster contains LZ-GCBC cells (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). Within this cluster, apart from the high expression of genes associated with the previously described LZ cluster, the cells start to express very specific genes such as MYC, MIR155HG or genes related to NF-kB pathway (i.e. NFKB1, NFKB2, NFKBIA, NFKBID, RELB). This transient expression of MYC has been described in LZ cells re-entering into the DZ, to continue with additional rounds of affinity maturation (Dominguez-Sola et al., 2012). Additionally, as compared to the LZ cluster, this cluster shows higher expression of BATF, a gene known to be involved in regulating AIDCA (a DZ marker) (Ise et al., 2011). From the scATAC-seq perspective, this LZ-DZ re-entry cluster is associated with epigenetic programming, with transiently increased chromatin accessibility associated with TFs of the NF-kB family as well as BATF. Altogether, these observations suggest that this cluster contains LZ cells that are already committed and preparing to return to the DZ." "CD83,MYC,MIR155HG,NFKB1,NFKB2,NFKBIA,NFKBID,RELB,BATF,MYC" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Dominguez-Sola2012|10.1038/ni.2428;Ise2011|10.1038/ni.2037" "gcbc_umap.png" NA
"LZ-proliferative" "GCBC" "LZ-proliferative" "This cluster has a proliferative signature, marked for example by upregulation of MCM gene family, PCNA, POLA1 (Bar-Joseph et al., 2008), while still maintaining the expression of standard light zone markers, like CD83 and LMO2. Furthermore, these cells maintain the expression of specific genes related to the LZ-DZ re-entry commitment cluster, such as BCL2A1, MIR155HG, NF-kB pathway genes or BATF. Therefore, this cluster may represent LZ cells that are starting to proliferate (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018)." "CD83,LMO2,MCM5,MCM7,MCM4,MCM6,PCNA,POLA,BCL2A1,MIR155HG,BATF" "Bar-Joseph2008|10.1073/pnas.0704723105;King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4" "gcbc_umap.png" NA
"LZ-DZ transition" "GCBC" "LZ-DZ transition" "This proliferative cluster presents intermediate expression of both LZ and DZ markers, i.e. containing traces of both CD83 and CXCR4 expression (King et al., 2021; Holmes et al., 2023; Milpied et al., 2018). It also downregulates previously mentioned signature related to LZ-DZ re-entry commitment, but cell cycle genes are highly expressed (Bar-Joseph et al., 2008). Therefore, these cells may represent the intermediate transitional step from proliferative LZ to proliferative DZ cells. It also suggests that the phenotypic switch from LZ to DZ occurs while cells proliferate." "CD83,CXCR4,MME,LMO2,POLA1,MKI67,TOP2A,CDC20,CCNB1" "King2021|10.1126/sciimmunol.abe6291;Holmes2020|10.1084/jem.20200483;Milpied2018|10.1038/s41590-018-0181-4;Bar-Joseph2008|10.1073/pnas.0704723105" "gcbc_umap.png" NA
"Precursor MBC" "GCBC" "Precursor MBC" "Within the level 1 cluster containing GCBCs, we also identified a subset of cells that were characterized by MBC-related markers while maintaining a non-proliferative GC signature. Specifically, this cluster was characterized by high expression of CCR6 or CELF2, genes that are commonly used in literature to define memory B cell precursors (Holmes et al., 2020). Although this cluster likely represents early MBCs derived from the LZ, we cannot exclude some technical issues or even MBC-GC doublet cells." "CCR6,CELF2,CXCR4,FOXP1" "Holmes2020|10.1084/jem.20200483" "gcbc_umap.png" NA
"Reactivated proliferative MBC" "GCBC" "Reactivated proliferative MBC" "This is a second cluster within the GC compartment that contains MBC markers. In this case, cells show high expression of BANK1 and TNFRSF13B (CD267). However, in the contrary to precursor MBC (that supposedly are generated from non-proliferative LZ cells), this cluster is characterized by high proliferation signature (i.e. PCNA, MKi67 or TOP2A expression; Bar-Joseph et al., 2008). Therefore, we hypothesize that these cells may be derived from secondary immune responses, in which MBC are reactivated, start to rapidly proliferate and may eventually differentiate into plasma cells (Moran et al., 2018). However, the overlap between some GC and MBC markers does not allow us to unequivocally exclude doublets." "BANK1,TNFRSF13B,PCNA,MKi67,TOP2A" "Bar-Joseph2008|10.1073/pnas.0704723105;Moran2018|10.1038/s41467-018-05772-7" "gcbc_umap.png" NA
"PC committed light zone GCBC" "GCBC" "PC committed light zone GCBC" "This subpopulation still belongs to the GCBCs level 1 cluster. It maintains high levels of B cell markers such as MS4A1 and PAX5, as well as high levels of GC markers such as BCL6, IRF8 and MEF2B, and LZ markers (MME (CD10), and CD83). However, it shows the first seeds of commitment towards PC differentiation, which are associated mostly with the expression, still at low levels, of the three key PC-related transcription factors PRDM1, XBP1 and IRF4 (Nutt et al., 2015)." "MS4A1,PAX5,BCL6,IRF8,MEF2B,PRDM1,XBP1,IRF4" "Nutt2015|10.1038/nri3795" "gcbc_umap.png" NA
"DZ migratory PC precursor" "PC" "DZ migratory PC precursor" "This cluster is composed by a relatively small number of cells that belong to the PC cluster at level 1, but in the PC-specific UMAP unexpectedly cluster close to both non-proliferative DZ-GCBCs and LZ-GCBCs (which were borrowed from the GCBC cluster). This intriguing cluster shows expression of GC markers such as BCL6, IRF8 and MEF2B, as well as intermediate levels of DZ (e.g.CXCR4 and AICDA) and LZ markers (e.g. CD83 and LMO2). Additionally, expression of B cell markers such as MS4A1 and PAX5 can be observed. These observations may be consistent with published evidence in mice suggesting that there are some maturing PCs migrating from the LZ to the DZ before leaving the GC (Kräutler et al., 2017). Although this hypothesis is attractive, we cannot formally rule out that these cells may represent doublets from PCs and GCBCs." "BCL6,IRF8,MEF2B,CXCR4,CD83,LMO2,MS4A1,PAX5,XBP1,SLAMF7" "Kräutler2017|10.1084/jem.20161533" "pc_umap.png" NA
"Early PC precursor" "PC" "Early PC precursor" "This cluster belongs to the PC level 1 cluster, and is located next to the PC-committed LZ-GCBCs. Although it still maintains the expression of B cell and GC markers, their levels are reduced as compared to the PC committed cells (e.g. MS4A1, BCL6, IRF8, CD83). On the contrary, the expression of the 3 PC transcription factors (PRDM1, XBP1 and IRF4) are increased as compared to PC committed cells, and the first traces of PC phenotypic markers can be detected, e.g. MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11 (Nutt et al., 2015)." "MS4A1,BCL6,IRF8,CD83,PRDM1,XBP1,IRF4,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11" "Nutt2015|10.1038/nri3795" "pc_umap.png" NA
"PB committed early PC precursor" "PC" "PB committed early PC precursor" "Similar expression profile to the Early PC precursors, with low levels of B cell and GC markers (e.g. MS4A1, BCL6, IRF8, CD83), high expression expression levels of the 3 PC transcription factors (PRDM1, XBP1 and IRF4) and traces of PC phenotypic markers, e.g. MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11. CD9, a marker for precursor PCs (Yoon et al., 2013), can be detected. However, in this cluster, low levels of some cell division-related genes such as H2AFZ and TUBA1B. Therefore, we interpret that these early PC precursors are already committed to become proliferative plasmablasts." "MS4A1,BCL6,IRF8,CD83,PRDM1,XBP1,IRF4,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CD9,TUBA1B" "Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"Transitional PB" "PC" "Transitional PB" "Cells in this cluster express the 3 PC transcription factors (PRDM1, XBP1 and IRF4) and PC phenotypic markers such as MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11 (Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013), can be detected. This is a peculiar cluster with intermediate levels of genes characteristic for proliferative plasmablasts such as H2AFZ, TUBA1B, MKI67 and TOP2A (Bar-Joseph et al., 2008). An analysis of cell cycle phases indicates that this cluster has cells both in S phase and G2M phase, which may suggest that it contains cells transitioning from PB committed early PC precursors to proliferative PBs and vice versa." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CD9,H2AFZ,TUBA1B,MKI67,TOP2A" "Bar-Joseph2008|10.1073/pnas.0704723105;Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"PB" "PC" "PB" "Cells within this cluster are clearly proliferative plasmablasts with high expression levels of proliferation-related genes (H2AFZ, TUBA1B, MKI67 and TOP2A, among others; Bar-Joseph et al., 2008). Otherwise have an expression pattern of PCs (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013), can be detected. As compared to transitional PBs, the expression levels of PC phenotypic markers are slightly increased. Traces of B cell markers can still be detected (e.g. MS4A1 and PAX5) and even some GC-related markers such as MEF2B." "H2AFZ,TUBA1B,MKI67,TOP2A,PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11" "Bar-Joseph2008|10.1073/pnas.0704723105;Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"IgG+ PC precursor" "PC" "IgG+ PC precursor" "Cells within this cluster have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013), can be detected.. Although the typical B cell-related genes (MS4A1 and PAX5, among others) are downregulated, some traces of MEF2B, a GC marker, can still be observed. Finally, as compared to early precursors, higher expression levels of IGHG can be detected in this cluster." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHG1,IGHG3,IGHG4" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"PreMature IgG+ PC" "PC" "PreMature IgG+ PC" "Cells within this cluster have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013) can still be detected. Although the typical B cell-related genes (MS4A1 and PAX5, among others) are downregulated, some traces of MEF2B, a GC marker, can still be observed. Finally, as compared to IgG+ PC precursors, higher expression levels of IGHG can be detected in this cluster" "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHG1,IGHG3,IGHG4" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"Mature IgG+ PC" "PC" "Mature IgG+ PC" "Cells within this cluster have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013) is downregulated, and CD44, a marker for mature PCs (Khodadadi et al., 2019), is expressed. Traces of MEF2B, a GC marker, or typical B-cell related genes (e.g. MS4A1) cannot be detected anymore. Finally, this subpopulation shows high expression levels of IGHG." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHG1,IGHG2,IGHG3,IGHG4,CD44" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102;Khodadadi2019|10.3389/fimmu.2019.00721" "pc_umap.png" NA
"MBC-derived IgG+ PC" "PC" "MBC-derived IgG+ PC" "Cells within this cluster have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013) is downregulated, and CD44, a marker for mature PCs (Khodadadi et al., 2019), is expressed. This subpopulation shows high expression levels of IGHG. Remarkably, cells in this cluster show expression of some markers expressed in MBCs, and in MBC-derived precursor PCs, such as FCMR and CCDC50. Therefore, the mature IgG+ PC phenotype together with traces of MBC-related genes made us think that this cluster represents mature IgG+ PCs derived from the reactivation of MBCs. Nevertheless, we cannot discard that these cells are doublets from MBC and PC." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHG1,IGHG2,IGHG3,IGHG4,CD44,CXCR4,FCMR,CCDC50" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102;Khodadadi2019|10.3389/fimmu.2019.00721" "pc_umap.png" NA
"Mature IgA+ PC" "PC" "Mature IgA+ PC" "Cells within this cluster have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013) is downregulated, and CD44, a marker for mature PCs (Khodadadi et al., 2019), is expressed. Traces of MEF2B, a GC marker, or typical B-cell related genes (e.g. MS4A1) cannot be detected anymore. Finally, this subpopulation shows high expression levels of IGHA." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CD44,IGHA1,IGHA2" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102;Khodadadi2019|10.3389/fimmu.2019.00721" "pc_umap.png" NA
"MBC-derived early PC precursor" "PC" "MBC-derived early PC precursor" "Cells within this cluster have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs is downregulated (Yoon et al., 2013), and CD44, a marker for mature PCs, is expressed (Khodadadi et al., 2019). This subpopulation shows high expression levels of IGHA. Remarkably, cells in this cluster show expression of some markers expressed in MBCs, and in MBC-derived precursor PCs, such FCMR and CCDC50. Therefore, the mature IgA+ PC phenotype together with traces of MBC-related genes made us think that this cluster represents mature IgA+ PCs derived from the reactivation of MBCs. Nevertheless, we cannot discard that these cells are doublets from MBC and PC." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CD44,IGHA1,IGHA2,CCDC50,FCMR" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102;Khodadadi2019|10.3389/fimmu.2019.00721" "pc_umap.png" NA
"MBC-derived PC precursor" "PC" "MBC-derived PC precursor" "This subpopulation clusters between MBC-derived early PC precursor and mature PCs. As compared to MBC-derived early PC precursor, these cells show higher levels of PC related genes (PRDM1, IRF4, XBP1, MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015), and increased levels of IG genes expression. Traces of B cell related genes are expressed such as MS4A1 and PAX5. Additionally, MBC-related genes are also expressed (i.e. FCMR and CCDC50). Therefore, due to the increased expression of PC and IG genes as compared to the MBC-derived early PC precursor, we interpret that this cluster represents a further step towards the phenotypic transformation of a MBC into a PC. Nevertheless, we cannot discard that these cells are doublets from MBC and PC." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CCDC50,FCMR,MS4A1,PAX5,IGHG3,IGHG4" "Nutt2015|10.1038/nri3795" "pc_umap.png" NA
"IgM+ early PC precursor" "PC" "IgM+ early PC precursor" "This cluster maps close to the early PC precursor cells but consistently show low expression levels of IGHM. The global gene expression pattern is similar to early PC precursor cells. It maintains low expression levels of B cell and GC markers, (e.g. MS4A1, BCL6, IRF8, CD83), and shows expression of the 3 PC transcription factors (PRDM1, XBP1 and IRF4) and the first traces of PC phenotypic markers can be detected, e.g. MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11 (Nutt et al., 2015)." "MS4A1,BCL6,IRF8,CD83,PRDM1,XBP1,IRF4,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHM" "Nutt2015|10.1038/nri3795" "pc_umap.png" NA
"IgM+ PC precursor" "PC" "IgM+ PC precursor" "Cells within this cluster express IGHM and have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11). CD9, a marker for precursor PCs (Yoon et al., 2013), can be detected. Although the typical B cell-related genes (MS4A1 and PAX5, among others) are downregulated, some traces of MEF2B, a GC marker, can still be observed. Finally, as compared to IgM+ early PC precursor, higher expression levels of IGHM can be detected (Nutt, et al. 2015)." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHM,CD9,MEF2B" "Nutt2015|10.1038/nri3795" "pc_umap.png" NA
"Premature IgM+ PC" "PC" "Premature IgM+ PC" "This IGHM-positive cluster show the expression of typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt, et al. 2015). CD9, a marker for precursor PCs (Yoon et al., 2013) is downregulated, and the expression of CD44, a marker for more mature PCs (Khodadadi et al., 2019), is increased. Finally, as compared to IgM+ PC precursor, higher expression levels of IGHM can be detected." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CD44,IGHM" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102;Khodadadi2019|10.3389/fimmu.2019.00721" "pc_umap.png" NA
"Mature IgM+ PC" "PC" "Mature IgM+ PC" "Cells within this cluster express IGHM and have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013) is downregulated. Traces typical B-cell related genes (e.g. MS4A1) cannot be detected. Finally, among the IgM+ clusters, this subpopulation shows the highest expression levels of IGHM." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,CD44,IGHM" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102;Khodadadi2019|10.3389/fimmu.2019.00721" "pc_umap.png" NA
"Short lived IgM+ PCs" "PC" "Short lived IgM+ PCs" "Cells within this cluster express IGHM and have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013), can also be detected. Although relatively similar to IgM+ PC precursor, this cluster shows a global gene downregulation with the exception of few upregulated genes strongly enriched in the endoplasmic reticulum cellular component concomitantly to high IgM expression. Therefore, we conclude that this may represent a subpopulation of short lived IgM PC cells that shut down most of the cellular functions with the exception of high production of IgM which is processed through the endoplasmic reticulum." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHM,CD9,MEF2B" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"IgD+ PC precursors" "PC" "IgD+ PC precursors" "Cells within this cluster express IGHD and have a typical PC markers (the 3 transcription factors PRDM1, IRF4 and XBP1, as well as phenotypic markers MZB1, SLAMF7, SSR4, CREB3L2 and FKBP11; Nutt et al., 2015). CD9, a marker for precursor PCs (Yoon et al., 2013), can be detected. Although the typical B cell-related genes (MS4A1 and PAX5, among others) are downregulated, some traces of MEF2B, a GC marker, can still be observed." "PRDM1,IRF4,XBP1,MZB1,SLAMF7,SSR4,CREB3L2,FKBP11,IGHD,MEF2B" "Nutt2015|10.1038/nri3795;Yoon2013|10.1016/j.bbrc.2012.12.102" "pc_umap.png" NA
"DC1 precursor" "Myeloid" "DC1 precursor" "DC1 corresponds to the cross-presenting conventional DC1 (cDC1, CD141+ DC, BDCA-3), which was reclassified by (Villani et al., 2017) as DC1 using scRNA-seq. This cluster is best marked by CLEC9A, and the top gene markers are: CLEC9A,IDO1, CADM1, CST3, SNX3, C1orf54, HLA-DPB1, IRF8, CCND1 and HLA-DPA1. The low levels of XCR1 together with an increased proliferation signature with respect to DC1 mature cells identify this population as a DC1 precursor (Balan et al., 2018, Villani et al., 2017)." "CLEC9A,IDO1,CADM1,CST3,SNX3,C1orf54,HLA-DPB1,IRF8,CCND1,HLA-DPA1" "Balan2018|10.1016/j.celrep.2018.07.033;Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"DC1 mature" "Myeloid" "DC1 mature" "This cluster had a similar profile to DC1 precursor, expressing higher levels of CLEC9A and XCR1, and acquiring a mature phenotype. DC1 mature cells had fewer cells in S or G2M phase and a decreased proliferation signature as compared to DC1 precursors (Balan et al., 2018, Villani et al., 2017)." "XCR1,CLEC9A,IDO1,CADM1,CST3,SNX3,C1orf54,HLA-DPB1,IRF8,CCND1,HLA-DPA1" "Balan2018|10.1016/j.celrep.2018.07.033;Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"DC2" "Myeloid" "DC2" "Conventional DC2 (cDC2, CD1C+ DC, BDCA-1) were reclassified by (Villani et al., 2017) as DC2 (expressing MHC class II genes) and DC3 (monocyte-like and inflammatory genes) using scRNA-seq. CD1C was the main marker and unique that identified both DC2 and DC3 clusters. This subpopulation expressed high levels of CD1C, CLEC10A, FCER1A, HLA-DQB1, HLA-DRB1, HLA-DQA1 and HLA-DPB1. This higher expression of MHC class II genes differentiates this population from DC3 (Villani et al., 2017)." "CD1C,CLEC10A,FCER1A,HLA-DQB1,HLA-DRB1,HLA-DQA1,HLA-DPB1" "Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"DC3" "Myeloid" "DC3" "Conventional DC2 (cDC2, CD1C+ DC, BDCA-1) were reclassified by (Villani et al., 2017) as DC2 (expressing MHC class II genes) and DC3 (monocyte-like and inflammatory genes) using scRNA-seq. The higher expression CD1C identified these populations as the second cluster of CD1C DC cells. This cluster expressed CD1C, CLEC10A, FCER1A, S100A8, S100A9, VCAN, LYZ and ANXA1. This inflammatory signature classified this subpopulation as a different one compared with DC2 that had more antigen presentation features (Villani et al., 2017)." "CD1C,CLEC10A,FCER1A,S100A8,S100A9,VCAN,LYZ,ANXA1" "Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"DC4" "Myeloid" "DC4" "DC4 corresponds to CD1C–CD141–CD11C+ DC, which is best marked by CD16 (encoded by FCGR3A) and shares signatures with monocytes. DC4 might differentiate from non-classical monocytes (CD16+). This cluster expressed FCGR3A, FTL, SIGLEC10, SERPINA1, LST1 and AIF1 and it was CD1C- (Villani et al., 2017)." "FCGR3A,FTL,SIGLEC10,SERPINA1,LST1,AIF1" "Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"DC5" "Myeloid" "DC5" "This cluster represents “AS DCs” (AXL+ SIGLEC6+ DCs). DC5 share marker genes with cDC and with plasmacytoid DC. This subpopulation had as top marker genes SIGLEC6, AXL, CDH1, CD22 and LILRA4 (Villani et al., 2017)." "SIGLEC6,AXL,CDH1,CD22,LILRA4" "Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"IL7R DC" "Myeloid" "IL7R DC" "This cluster was identified for its higher expression of IL7R and the expression of: NR4A3, CLDN1, NRARP, CLEC10A, AXL, and IL4I1. This cluster might represent pDC or DC5 precursors, but additional studies are needed to characterize this better (Rodrigues et al., 2018)." "IL7R,NR4A3,CLDN1,NRARP,CLEC10A,AXL,IL4I1" "Rodrigues2018|10.1038/s41590-018-0136-9" "myeloid_umap.png" NA
"aDC1" "Myeloid" "aDC1" "aDC1, aDC2 and aDC3 are three subtypes of CCR7+ activated DC that were recently annotated in the thymus atlas by (Park et al., 2020). aDC1 top markers were SLCO5A1, CCR7, DUSP5, LAD1, TREML1 and LAMP3. Contrary to the thymus atlas, we could not assign aDC1 to DC1." "CCR7,SLCO5A1,DUSP5,LAD1,TREML1,LAMP3" "Park2020|10.1126/science.aay3224" "myeloid_umap.png" NA
"aDC2" "Myeloid" "aDC2" "aDC1, aDC2 and aDC3 are three subtypes of CCR7+ activated DC that were recently annotated in the thymus atlas by (Park et al., 2020). aDC2 top markers were PRDM16, CCNA1, SLC16A2, S100A2, AIRE and CCL22. Contrary to the thymus atlas, we could not assign aDC2 to DC2. This cluster was composed of very few cells, and thus we could not validate it in the validation cohort. Thus, future studies with more power are needed to confirm the presence of this cluster." "CCR7,PRDM16,CCNA1,SLC16A2,S100A2,AIRE,CCL22" "Park2020|10.1126/science.aay3224" "myeloid_umap.png" NA
"aDC3" "Myeloid" "aDC3" "aDC1, aDC2 and aDC3 are three subtypes of CCR7+ activated DC that were recently annotated in the thymus atlas by (Park et al., 2020). aDC3 top markers were CCL19, MARCKSL1, FSCN1, ACTG1, SYNPO, and TMSB10. Contrary to the thymus atlas, we could not assign aDC3 to DC3." "CCR7,CCL19,MARCKSL1,FSCN1,ACTG1,SYNPO,TMSB10" "Park2020|10.1126/science.aay3224" "myeloid_umap.png" NA
"M1 Macrophages" "Myeloid" "M1 Macrophages" "This population had a higher expression of CD68 and the top gene markers are an inflammatory signature of M1 profile. This cluster has top gene markers: CCL4, IL1B, CCL3, TNF, IL6, IL1A and PTX3 (Barros et al., 2013)." "CD68,CCL4,IL1B,CCL3,TNF,IL6,IL1A,PTX3" "Barros2013|10.1371/journal.pone.0080908" "myeloid_umap.png" NA
"Monocytes" "Myeloid" "Monocytes" "This cluster was identified by its expression of CD14 and the expression of canonical genes well described for monocytes. Top markers of this cluster: VCAN, S100A9, S100A8, FCN1, S100A4 and S100A12 (Villani et al., 2017)." "CD14,VCAN,S100A9,S100A8,FCN1,S100A4,S100A12" "Villani2017|10.1126/science.aah4573" "myeloid_umap.png" NA
"Mast" "Myeloid" "Mast" "This cluster has expressions of classical markers for Mast cells KIT, TPSAB1 and TPSB2. Top markers of this cluster were: TPSAB1, TPSB2, CPA3, MS4A2, LTC4S, HPGD, HPGDS and LMO4 (Wu et al., 2022a)" "TPSAB1,TPSB2,CPA3,MS4A2,LTC4S,HPGD,HPGDS,LMO4" "Wu2022|10.1182/bloodadvances.2022006969" "myeloid_umap.png" NA
"Neutrophils" "Myeloid" "Neutrophils" "This cluster expressed specific markers previously described for neutrophils. Top gene markers: CXCL8, G0S2, PI3, CCL3L1, FCGR3B, PTGS2, and IFITM2 (Travaglini et al., 2020; Williams et al., 2021)." "CXCL8,G0S2,PI3,CCL3L1,FCGR3B,PTGS2,IFITM2" "Travaglini2020|10.1038/s41586-020-2922-4.;Williams2021|10.1016/j.cell.2021.05.013" "myeloid_umap.png" NA
"Cycling" "Myeloid" "Cycling" "This cluster is characterized by a high proliferation signature expressing CCNB2, PCNA, MKi67 and TOP2A (Bar-Joseph et al., 2008)." "CCNB2,PCNA,MKi67,TOP2A" "Bar-Joseph2008|10.1073/pnas.0704723105" "myeloid_umap.png" NA
"MMP Slan-like" "Myeloid" "MMP Slan-like" "This cluster had a profile of tonsil slan+ cells expressing higher levels of MMP9, MMP12, MMP14, HLA-DRA, HLA-DRB, CCR1, FCGR2A, ADAMDEC1 and C1QC, and intermediate levels of NECTIN2 and FUCA1 (Bianchetto-Aguilera et al., 2020). Based on GO terms, these MMP slancytes could play a role in antigen presentation, activation and matrix remodeling (Hofer et al., 2015)." "MMP9,MMP12,MMP14,HLA-DRA,HLA-DRB,CCR1,FCGR2A,ADAMDEC1,C1QA,C1QB,C1QC" "Bianchetto-Aguilera2020|10.1096/fj.202000181R;Hofer2015|10.1182/blood-2015-06-651331" "myeloid_umap.png" NA
"C1Q Slan-like" "Myeloid" "C1Q Slan-like" "This cluster had higher levels of tonsil slan+ cells such as C1QC, APOE, and MMP9, and intermediate levels of FUCA1, APOC1 and ADAMDEC1. This cluster had a profile to respond to classical complement activation with higher expression of C1Q family genes: C1QC, C1QB and C1QA. Also, This cluster had a higher expression of MHC class II genes HLA-DQA1, HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1, demonstrating their potential role in antigen presentation (Bianchetto‐Aguilera et al., 2020)." "C1QC,C1QB,C1QA,HLA-DQA1,HLA-DRA,HLA-DRB1,HLA-DPA1,HLA-DPB1" "Bianchetto-Aguilera2020|10.1096/fj.202000181R" "myeloid_umap.png" NA
"SELENOP Slan-like" "Myeloid" "SELENOP Slan-like" "These SELENOP slan-like expressed a tonsil slan+ cell signature with high levels of SELENOP, FOLR2, PTGDS, FUCA1, APOE, and APOC1. This cluster expressed higher levels of CCL18 suggesting it can be involved in the recruitment of MMP slan-like via CCL18-CCR1 axis. This cluster had an OXPHOS related signature pointing out their possible metabolic role in tonsils (Bianchetto‐Aguilera et al., 2020)." "SELENOP,FOLR2,PTGDS,FUCA1,APOE,APOC1" "Bianchetto-Aguilera2020|10.1096/fj.202000181R" "myeloid_umap.png" NA
"ITGAX Slan-like" "Myeloid" "ITGAX Slan-like" "This cluster expressed tonsil slan+ cell markers: FUCA1, NR1H3, and APOE. This cluster has an inflammatory signature expressing ITGAX, ZEB2, IL6R and IL18. It also expressed MAF, MAFB, and MAFG (Bianchetto‐Aguilera et al., 2020)." "ITGAX,ZEB2,IL6R,IL18,JAK3,STAT2,MAF,MAFB,MAFG" "Bianchetto-Aguilera2020|10.1096/fj.202000181R" "myeloid_umap.png" NA
"Basal cells" "Epithelial" "Basal cells" "This cluster represents the basal layer of the squamous epithelium, characterized by the expression of the basal cytokeratins KRT5 and KRT14 (Williams et al., 2021)." "KRT5,KRT14,S100A2" "Williams2021|10.1016/j.cell.2021.05.013" "epithelial_umap.png" NA
"Surface keratinocytes" "Epithelial" "Surface keratinocytes" "Cells in this cluster represent the main bulk of the surface epithelium with expression of several cytokeratins (KRT4, KRT13, KRT78, KRT80), SPRR3, TMPRSS11B and TMPRSS2 (Williams et al., 2021)." "KRT4,KRT13,KRT78,KRT80,SPRR3,TMPRSS11B,TMPRSS2" "Williams2021|10.1016/j.cell.2021.05.013" "epithelial_umap.png" NA
"VEGFA+" "Epithelial" "VEGFA+" "Cells in this cluster express VEGFA, which has been shown to be expressed by subsets of epithelial cells in other organs (Ellis et al., 2020)." "VEGFA,MIR205HG,PAX1" "Ellis2020|10.1016/j.devcel.2020.01.009" "epithelial_umap.png" NA
"Outer surface" "Epithelial" "Outer surface" "These cells express several genes associated with cornification/keratinization like CNFN and SPRR2 genes and represent the outermost layer of the surface epithelium (Williams et al., 2021)." "LCE3A,LCE3D,LCE3E,SPRR2D,SPRR2E,CNFN" "Williams2021|10.1016/j.cell.2021.05.013" "epithelial_umap.png" NA
"FDCSP epithelium" "Epithelial" "FDCSP epithelium" "This cluster is characterized by the high expression of KRTDAP, CALML5, and FDCSP. FDCSP was discovered in 2002 as a marker highly specific to follicular dendritic cells (Marshall et al., 2002). In the same article, the authors reported a FDCSP-expressing population of leukocyte-infiltrated tonsil crypts. This cluster might reflect this cell type. Of note, the oral mucosa cell atlas also reported a population of FDCSP-expressing epithelial cells (Williams et al., 2021)." "FDCSP,KRTDAP,CALML5" "Marshall2002|10.4049/jimmunol.169.5.2381;Williams2021|10.1016/j.cell.2021.05.013" "epithelial_umap.png" NA
"Crypt" "Epithelial" "Crypt" "Cells in this cluster express KRT8 and genes involved in inflammatory responses (IL1B, IFI27) and represent the epithelial crypts of the tonsils. Also in these clusters are cells which express SPIB and MARCKSL1, two genes associated with microfold cells (M cells) (Kobayashi et al., 2019)." "KRT8,IL1B,IFI27,SPIB,MARCKSL1" "Kobayashi2019|10.3389/fimmu.2019.02345" "epithelial_umap.png" NA
"FDC" "FDC" "FDC" "This is the main cluster of follicular dendritic cells, with high expression of the classical FDC markers FDCSP, CLU, CR2, and CXCL13 (Heesters et al., 2021)." "FDCSP,CLU,CR2,CXCL13" "Heesters2021|10.1084/jem.20210790" "fdc_umap.png" NA
"CD14+ CD55+ FDC" "FDC" "CD14+ CD55+ FDC" "This cluster, besides high expression levels of FDCSP, CLU and CXCL13, additionally expresses CD14 and CD55. CD14 expression in FDC is described in the literature as an independent predictor of transformation in follicular lymphoma (Smeltzer et al., 2014)." "FDCSP,CLU,CR2,CXCL13,CD14,CD55" "Smeltzer2014|10.1158/1078-0432.CCR-13-2367" "fdc_umap.png" NA
"COL27A1+ FDC" "FDC" "COL27A1+ FDC" "Cells in this cluster show lower expression levels of FDCSP, CLU, CR2, and CXCL13 compared to the main FDC cluster and high expression of COL27A1 (Rodda et al., 2018)." "FDCSP,CLU,CR2,CXCL13,COL27A1" "Rodda2018|10.1016/j.immuni.2018.04.006" "fdc_umap.png" NA
"FRC" "FDC" "FRC" "This cluster expresses CCL20, PERP, S100A2 and S100A9 markers associated with fibroblastic reticular cells (Rodda et al., 2018; Heesters et al., 2021)." "CCL20,PERP,S100A2,S100A9" "Rodda2018|10.1016/j.immuni.2018.04.006;Heesters2021|10.1084/jem.20210790" "fdc_umap.png" NA
"MRC" "FDC" "MRC" "Cells in this cluster express several collagen genes (COL1A1, COL1A2, COL3A1, COL5A2, COL6A3, COL12A1), as well as DCN and PDGFRB. This cluster was annotated as marginal reticular cells according to recently published literature. Based on PDGFRB expression at least part of these cells might represent perivascular precursors, as described in the literature in murine models (Jiang et al., 2021; Heesters et al., 2021)." "DCN,PDGFRB,COL1A1,COL1A2,COL3A1,COL5A2,COL6A3,COL12A1" "Jiang2021|10.3389/fimmu.2021.730438;Heesters2021|10.1084/jem.20210790" "fdc_umap.png" NA
"unknown" "FDC" "unknown" "Cells in this cluster had as markers several genes from the KLF family (KLF2/4/6) as well as other markers such as EGR1, DUSP1, ZFP36, NFKBIZ, SELE, VMP1, ADAMTSL4-AS1, AC020916.1, AC007952.4. However, this cluster also showed as markers distinct stress signature responses such as FOS, JUN or NEAT1 and hence we did not know whether to exclude this cluster as it may be composed of poor-quality cells. Additional studies are needed to make sense of the identity of this cluster." "KLF2,KLF4,KLF6,EGR1,DUSP1,ZFP36,FOS,JUN" NA "fdc_umap.png" NA
"Cycling FDC" "FDC" "Cycling FDC" "This a cluster of follicular dendritic cells, with high expression of the classical FDC markers and a specific gene signature of cycling. The top expressed genes are: HIST1H4C, HMGB2, STMN1, H2AFZ, HMGB1, HMGN2, NUSAP1, TUBA1B and PTTG1. As we observed that the proliferative signature was a major driver of variance in scRNA-seq data, which caused (1) cells from different lineages to cluster together and (2) hindered biological heterogeneity in the other cluster, we show this population in Figure 1B, but exclude it from downstream analysis (Bar-Joseph et al., 2008)." "FDCSP,CLU,CR2,HIST1H4C,HMGB2,STMN1,H2AFZ,HMGB1,HMGN2,NUSAP1,TUBA1B,PTTG1" "Bar-Joseph2008|10.1073/pnas.0704723105" "fdc_umap.png" NA
