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P-selectin identifies molecularly and functionally aged long-term hematopoietic stem cells in Mus musculus C57BL/6 female mice

ABSTRACT: Aged hematopoietic stem cells (HSCs) display myeloid-biased differentiation and reduced regenerative potential. In this study, we uncover that P-selectin (Selp) marks a subset of aged HSCs with reduced repopulation capacity. This population of HSCs expresses a prominent aging transcriptome. Overexpression of Selp in young HSCs impaired long-term reconstitution potential and repressed erythropoiesis. We show that IL-1β is elevated in aged bone marrow and administration of IL-1β induces expression of Selp and other aging-associated genes in HSCs. Finally, we demonstrate that transplantation of aged HSCs into young recipients restores a young-like transcriptome, specifically by repressing pro-inflammatory pathways, highlighting the important role of the bone marrow microenvironment in HSC aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE194273 | GEO | 2023/01/02

REPOSITORIES: GEO

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