<i>Rbfox2</i> selectively governs hematopoietic stem cell self-renewal by regulating proteostasis.

ABSTRACT: Self-renewing hematopoietic stem cells (HSCs) generate all blood cells and give rise to long-term reconstitution of the hematopoietic system after transplantation, but the molecular mechanisms that specifically regulate HSCs remain poorly defined. Here, we found that HSCs displayed a distinct messenger RNA alternative splicing pattern and preferentially expressed Rbfox2, an alternative splicing regulator, compared with multipotent progenitors (MPPs). Deletion of Rbfox2 from the hematopoietic compartment specifically depleted HSCs, but not progenitors in the adult bone marrow. Rbfox1 did not function redundantly with Rbfox2 in HSCs. Mechanistically, Rbfox2 loss led to proteostasis stress, including increased protein synthesis rate and accumulated misfolded

SUBMITTER: Gao L 

PROVIDER: S-EPMC12674123 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature