Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment

Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs...