Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved
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.
Authors
- Sven Turkalj (ORCID: https://orcid.org/0009-0002-3377-1170)
- Marlen Metzner (ORCID: https://orcid.org/0000-0003-1806-0952)
- Supat Thongjuea (ORCID: https://orcid.org/0000-0002-9129-4694)
- Sally‐Ann Clark (ORCID: https://orcid.org/0000-0003-1720-7975)
- Yiran Meng (ORCID: https://orcid.org/0000-0002-9333-2383)
- Grigore Gafencu (ORCID: https://orcid.org/0000-0001-6369-3201)
- Claus Nerlov (ORCID: https://orcid.org/0000-0002-0544-735X)
- Ryan Beveridge (ORCID: https://orcid.org/0000-0001-8116-9390)
- Merve Aksöz (ORCID: https://orcid.org/0000-0002-6032-0909)
- Niels Asger Jakobsen (ORCID: https://orcid.org/0000-0002-5776-5085)
- Paresh Vyas (ORCID: https://orcid.org/0000-0003-3931-0914)
- Bilyana Stoilova (ORCID: https://orcid.org/0000-0001-6192-9145)
- Ying Zhang (ORCID: https://orcid.org/0000-0003-3764-7329)
- Mario Buono
Institutions
- MRC Weatherall Institute of Molecular Medicine (GB)
- Oxford BioMedica (United Kingdom) (GB)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1126/sciimmunol.adk3469
- Citations
- 27
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 6.31
Funders
- Medical Research Council
- Biotechnology and Biological Sciences Research Council