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

Author:

Aksöz Merve1ORCID,Gafencu Grigore-Aristide1ORCID,Stoilova Bilyana1ORCID,Buono Mario1,Zhang Ying1,Turkalj Sven1,Meng Yiran1ORCID,Jakobsen Niels Asger1ORCID,Metzner Marlen1ORCID,Clark Sally-Ann1ORCID,Beveridge Ryan1ORCID,Thongjuea Supat1ORCID,Vyas Paresh12ORCID,Nerlov Claus1ORCID

Affiliation:

1. MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

2. Oxford NIHR BRC Haematology Theme, University of Oxford, Oxford, UK.

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.

Publisher

American Association for the Advancement of Science (AAAS)

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