The E3 ubiquitin ligase Cul5 regulates hematopoietic stem cell function for steady-state hematopoiesis in mice.

ABSTRACT: The balance of hematopoietic stem cell (HSC) self-renewal versus differentiation is essential to ensure long-term repopulation capacity while allowing response to events that require increased hematopoietic output. Proliferation and differentiation of HSCs and their progeny are controlled by the JAK/STAT pathway downstream of cytokine signaling. E3 ubiquitin ligases, like Cullin 5 (CUL5), can regulate JAK/STAT signaling by degrading signaling intermediates. Here we report that mice lacking CUL5 in hematopoietic cells (Cul5Vav-Cre) have increased numbers of hematopoietic stem and progenitor cells (HSPCs), splenomegaly, and extramedullary hematopoiesis. Differentiation in Cul5Vav-Cre mice is myeloid- and megakaryocyte-biased, resulting in leukocytosis, anemia, and thrombocytosis. Cul5Vav-Cre

SUBMITTER: Tomishima SA 

PROVIDER: S-EPMC12404750 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature