Tracking hematopoietic stem cell aging reveals its heterogeneous composition

Analysis of the reporter mice of Clusterin, an aging HSC signature gene, reveals that its expression faithfully marks an HSC subset with enhanced propensity to myeloid/platelet-biased repopulation that predominantly expands with aging. In contrast, its absence identifies an HSC subset with balanced repopulation that represents the majority of young HSCs but is underrepresented with aging. Both HSC subsets retain long-term repopulation capacity but exhibit different output of mature blood lineages.