USP7 sustains hematopoietic stem cell homeostasis partially via PU.1 stabilization.

ABSTRACT: Hematopoietic stem cell (HSC) self-renewal and lineage commitment are tightly controlled by post-translational mechanisms, but the contribution of deubiquitination to these processes remains unclear. Here, we define ubiquitin-specific protease 7 (USP7) as a critical regulator of HSC maintenance and hematopoietic homeostasis. Conditional Usp7 deletion in murine HSCs triggered rapid stem cell depletion, multilineage cytopenias, and systemic hematopoietic failure. Usp7-deficient HSCs displayed defective quiescence, reduced competitive repopulation capacity, and aberrant lineage differentiation. Mechanistically, USP7 directly binds and deubiquitinates the transcription factor PU.1, shielding it from proteasomal degradation. Loss of USP7 destabilized PU.1, leading to suppressed ex

SUBMITTER: Shan H 

PROVIDER: S-EPMC12781850 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature