The long-term contribution of human hematopoietic stem cell (HSC) clones to different blood lineages needs to be assessed under steady-state conditions over time. Using retrospective phylogenetic analysis and prospective clonal mutational tracing of all major blood lineages, we show that some HSC clones contribute stably to all lineages, while others show stable, intrinsically programmed lineage restriction.
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References
Carrelha, J. et al. Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells. Nature 554, 106–111 (2018). This study identified a limited repertoire of stable, lineage-restricted HSCs through single-cell transplantation of HSCs from young adult mice.
Weeks, L. D. & Ebert, B. L. Causes and consequences of clonal hematopoiesis. Blood 142, 2235–2246 (2023). This review article explains the cellular origins of clonal hematopoiesis, its natural history and its association with disease.
Lee-Six, H. et al. Population dynamics of normal human blood inferred from somatic mutations. Nature 561, 473–478 (2018). This paper revealed the phylogenetic history of normal human blood through whole-genome sequencing of clones derived from single hematopoietic stem and progenitor cells.
Mitchell, E. et al. Clonal dynamics of haematopoiesis across the human lifespan. Nature 606, 343–350 (2022). This paper applied the same method used in ref. 3 to study humans of various ages, demonstrating that hematopoiesis changes from polyclonal to oligoclonal with aging.
Spencer Chapman, M. et al. Clonal dynamics after allogeneic haematopoietic cell transplantation. Nature 635, 926–934 (2024). This paper reported high concordance between the contribution of the white blood lineage of the same HSC clone tracked in the donor and recipient after allogeneic stem cell transplantation.
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This is a summary of: Yoshizato, T. et al. Stable clonal contribution of lineage-restricted stem cells to human hematopoiesis. Nat. Genet. https://doi.org/10.1038/s41588-025-02405-w (2025).
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Stable, intrinsically programmed lineage restriction of human hematopoietic stem cells. Nat Genet 57, 2958–2959 (2025). https://doi.org/10.1038/s41588-025-02425-6
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DOI: https://doi.org/10.1038/s41588-025-02425-6
