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Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved

Aksöz, Merve, Gafencu, Grigore-Aristide, Stoilova, Bilyana, Buono, Mario, Zhang, Ying, Turkalj, Sven, Meng, Yiran, Jakobsen, Niels Asger, Metzner, Marlen, Clark, Sally-Ann, Beveridge, Ryan, Thongjuea, Supat, Vyas, Paresh, Nerlov, Claus·2024·Science Immunology

Abstract

Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution.

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Cited by

Metadata

Authors
Aksöz, M., Gafencu, G.-A., Stoilova, B., Buono, M., Zhang, Y., Turkalj, S., Meng, Y., Jakobsen, N. A., Metzner, M., Clark, S.-A., Beveridge, R., Thongjuea, S., Vyas, P., & Nerlov, C.
Venue
Science Immunology
Published
2024-08-23
Volume
9
Issue
98
ISSN
2470-9468
Cited by
40
References
10
Language
en

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