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

Su TY, Hauenstein J, Somuncular E, Dumral Ö, Leonard E, Gustafsson C, Tzortzis E, Forlani A, Johansson AS, Qian H, Månsson R, Luc S

Nat Commun 15 (1) 7966 [2024-09-11; online 2024-09-11]

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.

Bioinformatics Support for Computational Resources [Service]

PubMed 39261515

DOI 10.1038/s41467-024-52318-1

Crossref 10.1038/s41467-024-52318-1

pmc: PMC11391069
pii: 10.1038/s41467-024-52318-1