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Furtwangler, B.* ; Uresin, N.* ; Richter, S. ; Schuster, M.B.* ; Barmpouri, D.* ; Holze, H.* ; Wenzel, A.* ; Grønbæk, K.* ; Theilgaard-Mönch, K.* ; Theis, F.J. ; Schoof, E.M.* ; Porse, B.T.*

Mapping early human blood cell differentiation using single-cell proteomics and transcriptomics.

Science 390:eadr8785 (2025)

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Closed: Publ. Version/Full Text online available 10/2026

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Single-cell transcriptomics (scRNA-seq) has facilitated the characterization of cell state heterogeneity and recapitulation of differentiation trajectories. However, the exclusive use of mRNA measurements comes at the risk of missing important biological information. Here we leveraged recent technological advances in single-cell proteomics by Mass Spectrometry (scp-MS) to generate an scp-MS dataset of an in vivo differentiation hierarchy encompassing over 2500 human CD34+ hematopoietic stem and progenitor cells. Through integration with scRNA-seq, we identified proteins that are important for stem cell function, which were not indicated by their mRNA transcripts. Further, we showed that modeling translation dynamics can infer cell progression during differentiation and explain substantially more protein variation from mRNA than linear correlation. Our work offers a framework for single-cell multi-omics studies across biological systems.

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Publication type Article: Journal article

Document type Scientific Article

Keywords Blood Cell; Hematopoietic Stem-cells; Progenitor Cells; Expression; Rna; Protein; Hscs

ISSN (print) / ISBN 0036-8075

e-ISSN 1095-9203

Journal Science

Quellenangaben Volume: 390, Issue: 6770, Article Number: eadr8785

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants
Novo Nordisk Foundation
Helmholtz Association
Svend Andersen Foundation
Candys Foundation
Danish Cancer Society
Eva and Henry Fraenkel Memorial Foundation
Independent Research Fund Denmark
Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem)
Greater Copenhagen Health Science Partners
Lundbeck Foundation