Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells

Aksoz, M.; Gafencu, G.-A.; Stoilova, B. S.; Buono, M.; Meng, Y.; Jakobsen, N. A.; Metzner, M.; Clark, S.-A.; Beveridge, R.; Thongjuea, S.; Vyas, P.; Nerlov, C.

doi:10.1101/2022.01.14.475546

bioRxiv · 10.1101/2022.01.14.475546

Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells

Aksoz, M.·Gafencu, G.-A.·Stoilova, B. S.·Buono, M.·Meng, Y.·Jakobsen, N. A.·Metzner, M.·Clark, S.-A.·Beveridge, R.·Thongjuea, S.·Vyas, P.·Nerlov, C.

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Abstract

Hematopoietic stem cells (HSC) reconstitute multi-lineage human hematopoiesis after clinical bone marrow transplantation and are the cells-of-origin of hematological malignancies. Though HSC provide multi-lineage engraftment, individual murine HSCs are lineage-biased and contribute unequally to blood cell lineages. Now, by combining xenografting of molecularly barcoded adult human bone marrow (BM) HSCs and high-throughput single cell RNA sequencing we demonstrate that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identify platelet-biased and multi-lineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young, and aged, BM show that both the proportion of platelet-biased HSCs, and their level of transcriptional platelet priming, increases with age. Therefore, platelet-biased HSCs, as well as their increased prevalence and elevated transcriptional platelet priming during ageing, are conserved between human and murine hematopoiesis. One-Sentence SummaryIn vivo barcoding and single cell RNA sequencing identifies platelet-biased human bone marrow HSCs.

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Aksoz, M., Gafencu, G.-A., Stoilova, B. S., Buono, M., Meng, Y., Jakobsen, N. A., Metzner, M., Clark, S.-A., Beveridge, R., Thongjuea, S., Vyas, P., Nerlov, C.. 2022-01-14. Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells. https://doi.org/10.1101/2022.01.14.475546

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