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Rejuvenation of aged HSCs by reactivation of Lin28b during ex vivo culture [Bulk RNA-seq]

ABSTRACT: Self-renewing multipotent hematopoietic stem cells support life-long hematopoiesis and can reconstitute the entire blood system following transplantation. Aging is associated with a buildup of immunophenotypic HSCs that have weak or lack reconstitution activity. We have previously established a polymer-based HSC culture system that can robustly expand transplantable bone marrow-derived HSCs from young adult mice. However, the mechanism of the system remains unknown as does its potential to expand HSCs from different stages of ontogeny. Here we compared ex vivo HSC expansion from the fetal liver, young bone marrow, and aged bone marrow at the functional and molecular levels. We find that expression of the fetal-specific gene Lin28b inversely correlates with reconstitution potential, with Lin28b more highly expressed in expanded FL and young BM cultures. By contrast, aged BM cultures display low levels of Lin28b expression and fail to stably reconstitute the hematopoietic system following transplantation. Consistent with a functional role for this fetal program in ex vivo expanded HSCs, Lin28b-deficient bone marrow displayed age-associated features. Importantly, overexpression of Lin28b during ex vivo expansion is sufficient to enhance reconstitution potential, suggesting novel opportunities for rejuvenation of aged HSC. In summary, we report a functional and molecular characterization of the age-associated changes in ex vivo HSC expansion potential and identify Lin28b as an important regulator of functional HSC expansion ex vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE292172 | GEO | 2026/09/30

REPOSITORIES: GEO

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Rejuvenation of aged HSCs by reactivation of Lin28b during ex vivo culture [Multiome]

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