Single-cell and spatial transcriptomics
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High-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs identifies platelet-biased and multilineage human HSCs and demonstrates that age-associated HSC platelet bias is evolutionarily conserved.
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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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@article{Aksz2024Hematopoietic,
title = {Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved},
author = {Merve Aksöz and Grigore Gafencu and Bilyana Stoilova and Mario Buono and Ying Zhang and Sven Turkalj and Yiran Meng and Niels Asger Jakobsen and Marlen Metzner and Sally‐Ann Clark and Ryan Beveridge and Supat Thongjuea and Paresh Vyas and Claus Nerlov},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adk3469},
url = {https://doi.org/10.1126/sciimmunol.adk3469}
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