GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE215nnn/GSE215923/primaryOK200TranscriptomicsMus musculus Genome binding/occupancy profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE215923GEOGSEfalseHematopoietic stem cell sex-dimorphism intensifies aging phenotypes and downstream hematopoiesisHematopoietic 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.2026/09/09GSE215923GSM9229211GSM9229210GSM9229199GSM9229213GSM9229212GSM9229215GSM9229214GSM9229192GSM9229191GSM9229194GSM9229193GSM9229196GSM9229195GSM9229198GSM9229197GSM6647496GSM6647495GSM6647497GSM6647492GSM6647494GSM9229190GSM6647493GSM9229208GSM9229207GSM9229209GSM9229200GSM9229202GSM9229201GSM9229204GSM9229203GSM9229206GSM92292051702124247215923Mus musculus[42618695]