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Cited by 195Single-cell and spatial transcriptomicsAdvanced Proteomics Techniques and ApplicationsMonoclonal and Polyclonal Antibodies Research

Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states

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Triana, Sergio, Vonficht, Dominik, Jopp-Saile, Lea, Raffel, Simon, Lutz, Raphael, Leonce, Daniel, Antes, Magdalena, Hernández-Malmierca, Pablo +14 more·2021·Nature Immunology
DOI 10.1038/s41590-021-01059-0PMC PMC8642243

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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.

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  • The CITE-seq-based FACS sorting scheme stratified the differentiation cultures into seven defined cell states after four days of culture.

    “Thereby, we stratified the cultures into seven defined cell states after four days of culture.”

    From Design principles of cell-state-specific enhancers in hematopoiesis (2025) · cites this paper as [68]

    The Results section, “A data-defined gating scheme for human hematopoiesis” (page unavailable), describes a single-cell-data-derived FACS gating scheme for molecularly defined cell states. It defines 14 states, however, and does not report stratifying differentiation cultures into seven states after four days; the Methods section, “Single-cell index cell cultures” (page unavailable), describes cultures lasting 16–19 days. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Other RFX members such as RFX1 and RFX8 have been demonstrated to regulate MHC class II expression.

    “Although RFX2/3 are not well characterized in hematopoiesis, other RFX members such as RFX1 and RFX8 have been demonstrated to regulate MHC class II expression 35-37 .”

    From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [35]

    The Results passages on surface markers and data-driven flow cytometry discuss hematopoietic cell states, but do not address RFX1 or RFX8 regulation of MHC class II. Further searches for those factors and for MHC class II found no passage supporting the attributed claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Other RFX members have been demonstrated to regulate MHC class II expression.

    “as other RFX members have been demonstrated to regulate MHC class II expression 35,64”

    From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [35]

    The Results passages on surface markers and immune-cell populations do not discuss RFX proteins regulating MHC class II expression. Searches of our copy for RFX members and MHC class II regulation returned no passage addressing the claim. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Authors
Triana, S., Vonficht, D., Jopp-Saile, L., Raffel, S., Lutz, R., Leonce, D., Antes, M., Hernández-Malmierca, P., Ordoñez-Rueda, D., Ramasz, B., Boch, T., Jann, J.-C., Nowak, D., Hofmann, W.-K., Müller-Tidow, C., Hübschmann, D., Alexandrov, T., Benes, V., Trumpp, A., Paulsen, M., Velten, L., & Haas, S.
Affiliations
  • Heidelberg University (DE)
  • German Cancer Research Center (DE)
  • University Hospital Heidelberg (DE)
  • European Molecular Biology Laboratory (DE)
  • University of California San Diego (US)
  • Novo Nordisk Foundation (DK)
  • Universitat Pompeu Fabra (ES)
Corresponding author
  • Velten, Lars
  • Haas, Simon
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2021-11-22
Volume
22
Issue
12
Pages
1577-1589
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/s41590-021-01059-0
PMC
PMC8642243
OpenAlex
W3215605010
Cited by
195
References
15
Citations by year
2026: 38 · 2025: 45 · 2024: 43 · 2023: 32 · 2022: 33 · 2021: 4
FWCI
9.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
Funders
  • Deutsches Krebsforschungszentrum
  • Ministerio de Ciencia, Innovación y Universidades (PID2019)
  • Centres de Recerca de Catalunya
  • Gutermuth Foundation
  • Deutsche Forschungsgemeinschaft (FOR2033, FOR 2674, SFB873)
  • Bundesministerium für Bildung und Forschung (01ZX1911D)
  • Generalitat de Catalunya (PID2019)
  • Ministerio de Ciencia e Innovación (PID2019)
  • José Carreras Leukämie-Stiftung (DJCLS H 03/01)
  • Deutsche Krebshilfe
  • Darwin Trust of Edinburgh
  • Agencia Estatal de Investigación (PID2019)
  • H2020 European Research Council (773089)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
reference map, surface marker expression, flow cytometry, bone marrow, human blood, healthy aging, leukemia, cell identity
MeSH terms
Healthy Aging, RNA-Seq, Age Factors, Blood Cells, Bone Marrow Cells, Cell Separation, Cells, Cultured, Flow Cytometry, Humans, Leukemia, Proteome, Gene Expression Profiling, Databases, Genetic, Proteomics, Systems Biology, Single-Cell Analysis, Transcriptome

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