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Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets

Author

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  • Tsu-Yi Su

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Julia Hauenstein

    (Karolinska Institutet)

  • Ece Somuncular

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Özge Dumral

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Elory Leonard

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Charlotte Gustafsson

    (Karolinska Institutet)

  • Efthymios Tzortzis

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Aurora Forlani

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Anne-Sofie Johansson

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet)

  • Hong Qian

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet
    Karolinska University Hospital)

  • Robert Månsson

    (Karolinska Institutet
    Karolinska University Hospital
    KTH Royal Institute of Technology)

  • Sidinh Luc

    (Center for Hematology and Regenerative Medicine
    Karolinska Institutet
    Karolinska University Hospital)

Abstract

Age is a risk factor for hematologic malignancies. Attributes of the aging hematopoietic system include increased myelopoiesis, impaired adaptive immunity, and a functional decline of the hematopoietic stem cells (HSCs) that maintain hematopoiesis. Changes in the composition of diverse HSC subsets have been suggested to be responsible for age-related alterations, however, the underlying regulatory mechanisms are incompletely understood in the context of HSC heterogeneity. In this study, we investigated how distinct HSC subsets, separated by CD49b, functionally and molecularly change their behavior with age. We demonstrate that the lineage differentiation of both lymphoid-biased and myeloid-biased HSC subsets progressively shifts to a higher myeloid cellular output during aging. In parallel, we show that HSCs selectively undergo age-dependent gene expression and gene regulatory changes in a progressive manner, which is initiated already in the juvenile stage. Overall, our studies suggest that aging intrinsically alters both cellular and molecular properties of HSCs.

Suggested Citation

  • Tsu-Yi Su & Julia Hauenstein & Ece Somuncular & Özge Dumral & Elory Leonard & Charlotte Gustafsson & Efthymios Tzortzis & Aurora Forlani & Anne-Sofie Johansson & Hong Qian & Robert Månsson & Sidinh Lu, 2024. "Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52318-1
    DOI: 10.1038/s41467-024-52318-1
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    References listed on IDEAS

    as
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