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

Tsu-Yi Su, Julia Hauenstein, Ece Somuncular, Özge Dumral, Elory Leonard, Charlotte Gustafsson, Efthymios Tzortzis, Aurora Forlani, Anne-Sofie Johansson, Hong Qian, Robert Månsson and Sidinh Luc ()
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Tsu-Yi Su: Center for Hematology and Regenerative Medicine
Julia Hauenstein: Karolinska Institutet
Ece Somuncular: Center for Hematology and Regenerative Medicine
Özge Dumral: Center for Hematology and Regenerative Medicine
Elory Leonard: Center for Hematology and Regenerative Medicine
Charlotte Gustafsson: Karolinska Institutet
Efthymios Tzortzis: Center for Hematology and Regenerative Medicine
Aurora Forlani: Center for Hematology and Regenerative Medicine
Anne-Sofie Johansson: Center for Hematology and Regenerative Medicine
Hong Qian: Center for Hematology and Regenerative Medicine
Robert Månsson: Karolinska Institutet
Sidinh Luc: Center for Hematology and Regenerative Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52318-1

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