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Hematopoietic stem cell sex-dimorphism intensifies aging phenotypes and downstream hematopoiesis

ABSTRACT: Hematopoietic stem cells (HSCs) sustain blood and immune production throughout life and are central to aging and disease. Yet, most studies of HSC aging rely on male mice, leaving sex-specific trajectories poorly defined. We profiled HSC aging across the lifespan in male and female mice using multi-omic analyses and over 820 animals. Two patterns emerged. In males, HSCs continue to remodel after mid-life, showing progressive accumulation of CD150^high myeloid-biased cells, widespread transcriptional shifts, and chromatin reprogramming. In females, HSC changes plateau earlier but exhibit greater inter-individual variability. Integration of RNA-seq, ATAC-seq, and single-cell data implies GATA, RUNX, and Sema4a as key factors. Surprisingly, transplantation studies revealed that many sex-dependent phenotypes are overridden by the host environment. These findings define distinct, sex-specific trajectories of hematopoietic aging and provide a comprehensive resource to guide mechanistic studies and inform sex-tailored therapeutic strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE215923 | GEO | 2026/09/09

REPOSITORIES: GEO

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