Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states
Sergio Triana, Dominik Vonficht, Lea Jopp-Saile, Simon Raffel, Raphael Lutz, Daniel Leonce, Magdalena Antes, Pablo Hernández-Malmierca, Diana Ordoñez-Rueda, Beáta Ramasz, Tobias Boch, Johann-Christoph Jann, Daniel Nowak, Wolf-Karsten Hofmann, Carsten Müller-Tidow, Daniel Hübschmann, Theodore Alexandrov, Vladimir Benes, Andreas Trumpp, Malte Paulsen, Lars Velten, Simon Haas
Abstract
Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all main hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables the functional capacities of precisely mapped cell states to be measured at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.
Datasets
1. 3 healthy young and 3 healthy old bone marrow donors (Reference sample)
Metadata
donor_id
ClusterID
BM_type
Cell_label
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
assay_ontology_term_id
tissue_ontology_term_id
Genotype
development_stage_ontology_term_id
sex_ontology_term_id
disease_ontology_term_id
cell_type_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
CD56dimCD16+ NK cells5112 cells CD4+ memory T cells4555 cells Mature naive B cells4068 cells CD8+ effector memory T cells3769 cells Classical Monocytes3083 cells Nonswitched memory B cells2811 cells CD8+ central memory T cells2364 cells Early erythroid progenitor1950 cells Late erythroid progenitor1887 cells CD8+CD103+ tissue resident memory T cells1886 cells Lymphomyeloid prog1454 cells Class switched memory B cells1449 cells Conventional dendritic cell 11180 cells Non-classical monocytes996 cells Early promyelocytes947 cells Late promyelocytes712 cells GammaDelta T cells667 cells Megakaryocyte progenitors666 cells Conventional dendritic cell 2586 cells Plasmacytoid dendritic cell progenitors571 cells CD4+ naive T cells505 cells Erythro-myeloid progenitors492 cells Immature B cells466 cells CD4+ cytotoxic T cells418 cells Plasmacytoid dendritic cells344 cells CD8+ naive T cells339 cells CD56brightCD16- NK cells300 cells Eosinophil-basophil-mast cell progenitors199 cells Aberrant erythroid182 cells CD11c+ memory B cells103 cells CD69+PD-1+ memory CD4+ T cells52 cells NK cell progenitors26 cells Mesenchymal cells_117 cells Monocyte-like blasts2 cells Mesenchymal cells_21 cells NCBITaxon:960649057 cells UBERON:000237149057 cells HsapDv:000012011317 cells HsapDv:000015910639 cells CD16-positive, CD56-dim natural killer cell, human5112 cells CD4-positive, alpha-beta memory T cell4607 cells erythroid progenitor cell3837 cells effector memory CD8-positive, alpha-beta T cell3769 cells classical monocyte3083 cells unswitched memory B cell2811 cells central memory CD8-positive, alpha-beta T cell2364 cells hematopoietic multipotent progenitor cell1908 cells CD8-positive, alpha-beta memory T cell1886 cells conventional dendritic cell1766 cells lymphoid lineage restricted progenitor cell1454 cells class switched memory B cell1449 cells non-classical monocyte996 cells early promyelocyte947 cells late promyelocyte712 cells gamma-delta T cell667 cells megakaryocyte progenitor cell666 cells common dendritic progenitor571 cells naive thymus-derived CD4-positive, alpha-beta T cell505 cells megakaryocyte-erythroid progenitor cell492 cells precursor B cell456 cells CD4-positive, alpha-beta cytotoxic T cell418 cells plasmacytoid dendritic cell344 cells naive thymus-derived CD8-positive, alpha-beta T cell339 cells CD16-negative, CD56-bright natural killer cell, human300 cells basophil mast progenitor cell199 cells erythroid lineage cell182 cells natural killer cell152 cells pre-natural killer cell26 cells fraction A pre-pro B cell17 cells small pre-B-II cell4 cells non-terminally differentiated cell2 cells BD Rhapsody Targeted mRNA49057 cells 26-year-old human stage11317 cells 65-year-old human stage10639 cells 25-year-old human stage9751 cells 34-year-old human stage6963 cells 69-year-old human stage6316 cells 59-year-old human stage4071 cells 2. 15 leukemic bone marrow donors
Metadata
Cluster_ID
donor_id
Sample_Tag
Cell_label
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
assay_ontology_term_id
tissue_ontology_term_id
Genotype
development_stage_ontology_term_id
sex_ontology_term_id
disease_ontology_term_id
cell_type_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Classical Monocytes9935 cells Early promyelocytes5106 cells CD4+ memory T cells1793 cells CD8+ effector memory T cells1773 cells CD8+ central memory T cells968 cells Late promyelocytes933 cells Lymphomyeloid prog913 cells CD8+CD103+ tissue resident memory T cells890 cells Conventional dendritic cell 2877 cells CD56dimCD16+ NK cells690 cells Non-classical monocytes552 cells Aberrant erythroid440 cells Mature naive B cells416 cells Nonswitched memory B cells322 cells GammaDelta T cells261 cells Late erythroid progenitor230 cells CD4+ naive T cells190 cells CD4+ cytotoxic T cells179 cells CD8+ naive T cells175 cells Conventional dendritic cell 1156 cells Class switched memory B cells94 cells Eosinophil-basophil-mast cell progenitors92 cells Erythro-myeloid progenitors89 cells Early erythroid progenitor64 cells Megakaryocyte progenitors62 cells Monocyte-like blasts55 cells Immature-like blasts25 cells CD11c+ memory B cells24 cells CD56brightCD16- NK cells23 cells Mesenchymal cells_119 cells Plasmacytoid dendritic cell progenitors16 cells CD69+PD-1+ memory CD4+ T cells13 cells Plasmacytoid dendritic cells10 cells NK cell progenitors2 cells Mesenchymal cells_21 cells NCBITaxon:960631586 cells UBERON:000237131586 cells FLT3-ITD,NPM1-mut16961 cells FLT3-wt,NPM1-mut10891 cells HsapDv:000014911941 cells classical monocyte9935 cells early promyelocyte5106 cells CD4-positive, alpha-beta memory T cell1806 cells effector memory CD8-positive, alpha-beta T cell1773 cells hematopoietic multipotent progenitor cell1373 cells conventional dendritic cell1033 cells central memory CD8-positive, alpha-beta T cell968 cells late promyelocyte933 cells lymphoid lineage restricted progenitor cell913 cells CD8-positive, alpha-beta memory T cell890 cells CD16-positive, CD56-dim natural killer cell, human690 cells non-classical monocyte552 cells erythroid lineage cell440 cells unswitched memory B cell322 cells erythroid progenitor cell294 cells gamma-delta T cell261 cells naive thymus-derived CD4-positive, alpha-beta T cell190 cells CD4-positive, alpha-beta cytotoxic T cell179 cells naive thymus-derived CD8-positive, alpha-beta T cell175 cells class switched memory B cell94 cells basophil mast progenitor cell92 cells megakaryocyte-erythroid progenitor cell89 cells non-terminally differentiated cell80 cells megakaryocyte progenitor cell62 cells CD16-negative, CD56-bright natural killer cell, human23 cells natural killer cell21 cells common dendritic progenitor16 cells plasmacytoid dendritic cell10 cells pre-natural killer cell2 cells fraction A pre-pro B cell1 cells BD Rhapsody Targeted mRNA31586 cells acute myeloid leukemia27852 cells acute promyelocytic leukemia3734 cells 55-year-old human stage11941 cells 61-year-old human stage7547 cells 44-year-old human stage4149 cells 56-year-old human stage1396 cells 62-year-old human stage1341 cells 70-year-old human stage880 cells 46-year-old human stage687 cells 78-year-old human stage607 cells 45-year-old human stage603 cells 71-year-old human stage565 cells 32-year-old human stage545 cells 54-year-old human stage527 cells 66-year-old human stage492 cells 51-year-old human stage306 cells 3. blood and bone marrow from a healthy young donor
Metadata
Cluster_ID
Sample
Cell_label
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
assay_ontology_term_id
tissue_ontology_term_id
Genotype
development_stage_ontology_term_id
sex_ontology_term_id
disease_ontology_term_id
donor_id
cell_type_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Classical Monocytes4815 cells CD56dimCD16+ NK cells1721 cells CD4+ memory T cells1640 cells Non-classical monocytes1590 cells Mature naive B cells974 cells CD8+ effector memory T cells623 cells CD8+CD103+ tissue resident memory T cells600 cells Nonswitched memory B cells596 cells Class switched memory B cells330 cells Conventional dendritic cell 2280 cells Early erythroid progenitor252 cells CD4+ naive T cells188 cells CD8+ central memory T cells187 cells CD8+ naive T cells165 cells Lymphomyeloid prog156 cells Late erythroid progenitor138 cells GammaDelta T cells109 cells Early promyelocytes106 cells CD56brightCD16- NK cells77 cells Conventional dendritic cell 172 cells Megakaryocyte progenitors57 cells Late promyelocytes54 cells Plasmacytoid dendritic cells46 cells Erythro-myeloid progenitors35 cells Eosinophil-basophil-mast cell progenitors33 cells Plasmacytoid dendritic cell progenitors18 cells Aberrant erythroid10 cells CD11c+ memory B cells6 cells CD69+PD-1+ memory CD4+ T cells5 cells Mesenchymal cells_13 cells CD4+ cytotoxic T cells3 cells NCBITaxon:960615502 cells HsapDv:000013515502 cells classical monocyte4815 cells CD16-positive, CD56-dim natural killer cell, human1721 cells CD4-positive, alpha-beta memory T cell1645 cells non-classical monocyte1590 cells effector memory CD8-positive, alpha-beta T cell623 cells CD8-positive, alpha-beta memory T cell600 cells unswitched memory B cell596 cells erythroid progenitor cell390 cells conventional dendritic cell352 cells class switched memory B cell330 cells naive thymus-derived CD4-positive, alpha-beta T cell188 cells central memory CD8-positive, alpha-beta T cell187 cells hematopoietic multipotent progenitor cell171 cells naive thymus-derived CD8-positive, alpha-beta T cell165 cells lymphoid lineage restricted progenitor cell156 cells gamma-delta T cell109 cells early promyelocyte106 cells CD16-negative, CD56-bright natural killer cell, human77 cells megakaryocyte progenitor cell57 cells late promyelocyte54 cells plasmacytoid dendritic cell46 cells megakaryocyte-erythroid progenitor cell35 cells basophil mast progenitor cell33 cells common dendritic progenitor18 cells erythroid lineage cell10 cells CD4-positive, alpha-beta cytotoxic T cell3 cells natural killer cell1 cells BD Rhapsody Targeted mRNA15502 cells 41-year-old human stage15502 cells 4. healthy young bone marrow donor
Metadata
Cluster_ID
donor_id
Cell_label
organism_ontology_term_id
self_reported_ethnicity_ontology_term_id
assay_ontology_term_id
tissue_ontology_term_id
Genotype
development_stage_ontology_term_id
sex_ontology_term_id
disease_ontology_term_id
cell_type_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Mature naive B cells2152 cells CD4+ memory T cells1736 cells CD8+CD103+ tissue resident memory T cells1037 cells CD56dimCD16+ NK cells760 cells Nonswitched memory B cells665 cells Lymphomyeloid prog452 cells CD8+ naive T cells413 cells Late promyelocytes380 cells Early promyelocytes369 cells Early erythroid progenitor333 cells Late erythroid progenitor318 cells CD4+ naive T cells285 cells CD8+ effector memory T cells263 cells Immature B cells242 cells Conventional dendritic cell 1237 cells CD8+ central memory T cells215 cells Erythro-myeloid progenitors214 cells Megakaryocyte progenitors181 cells Classical Monocytes163 cells Plasmacytoid dendritic cell progenitors145 cells CD56brightCD16- NK cells131 cells Class switched memory B cells130 cells Plasmacytoid dendritic cells103 cells Non-classical monocytes97 cells GammaDelta T cells92 cells Conventional dendritic cell 275 cells Eosinophil-basophil-mast cell progenitors59 cells NK cell progenitors11 cells CD69+PD-1+ memory CD4+ T cells6 cells Aberrant erythroid2 cells NCBITaxon:960613165 cells UBERON:000237113165 cells HsapDv:000012013165 cells CD4-positive, alpha-beta memory T cell1742 cells CD8-positive, alpha-beta memory T cell1037 cells hematopoietic multipotent progenitor cell805 cells CD16-positive, CD56-dim natural killer cell, human760 cells unswitched memory B cell665 cells erythroid progenitor cell651 cells lymphoid lineage restricted progenitor cell452 cells naive thymus-derived CD8-positive, alpha-beta T cell413 cells late promyelocyte380 cells early promyelocyte369 cells conventional dendritic cell312 cells naive thymus-derived CD4-positive, alpha-beta T cell285 cells effector memory CD8-positive, alpha-beta T cell263 cells central memory CD8-positive, alpha-beta T cell215 cells megakaryocyte-erythroid progenitor cell214 cells precursor B cell189 cells megakaryocyte progenitor cell181 cells classical monocyte163 cells common dendritic progenitor145 cells CD16-negative, CD56-bright natural killer cell, human131 cells class switched memory B cell130 cells plasmacytoid dendritic cell103 cells non-classical monocyte97 cells gamma-delta T cell92 cells basophil mast progenitor cell59 cells fraction A pre-pro B cell22 cells small pre-B-II cell12 cells pre-natural killer cell11 cells erythroid lineage cell2 cells natural killer cell1 cells BD Rhapsody Whole Transcriptome Analysis13165 cells 26-year-old human stage13165 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/93eebe82-d8c3-41bc-a906-63b5b5f24a9d
Alias names
EGAS00001005593, PMID34811546, PMC8642243
Cite this study
Triana, S., Vonficht, D., Jopp-Saile, L., Raffel, S., Lutz, R., Leonce, D., Antes, M., Hernández-Malmierca, P., Ordoñez-Rueda, D., Ramasz, B. and Boch, T., 2021. Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states. Nature immunology, 22(12), pp.1577-1589. https://doi.org/10.1038/s41590-021-01059-0
