The spliceosome factor sart3 regulates hematopoietic stem/progenitor cell development in zebrafish through the p53 pathway.

ABSTRACT: Hematopoietic stem cells (HSCs) possess the potential for self-renew and the capacity, throughout life, to differentiate into all blood cell lineages. Yet, the mechanistic basis for HSC development remains largely unknown. In this study, we characterized a zebrafish smu471 mutant with hematopoietic stem/progenitor cell (HSPC) defects and found that sart3 was the causative gene. RNA expression profiling of the sart3^smu471 mutant revealed spliceosome and p53 signaling pathway to be the most significantly enriched pathways in the sart3^smu471 mutant. Knock down of p53 rescued HSPC development in the sart3^smu471 mutant. Interestingly, the p53 inhibitor, mdm4, had undergone an alternative splicing event in the mutant. Restoration of mdm4 partially rescued HSPC de

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC8492694 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature