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Hematopoietic stem and progenitor cells have the capacity to self-renew and differentiate into all blood cell lineages, and thus sustain life-long homeostasis of the hematopoietic system. Although intensive studies have focused on the orchestrated genetic network of hematopoietic stem and progenitor cell specification and expansion, relatively little is known on the regulation of hematopoietic stem and progenitor cell survival during embryogenesis. Here, we generated two types of  miR-142a-3p  genetic mutants in zebrafish and showed that the loss-of-function mutants displayed severe reduction of hematopoietic stem and progenitor cells. Further analysis showed that the diminished proliferation and excessive apoptosis in  miR-142a-3p  mutants were attributed to the increased  p53  signaling. Mechanistically, we demonstrated that  miR-142a-3p  directly targets  p53  during hematopoietic stem and progenitor cell development, and the hematopoietic stem and progenitor cell survival defect in  miR-142a-3p  mutants could be rescued by loss of  p53 . Therefore, our work reveals the significance of the  miR-142a-3p - p53  pathway in controlling hematopoietic stem and progenitor cell survival, and thus advances our understanding of the role of  p53  in vertebrate hematopoiesis.

Direct regulation of p53 by miR-142a-3p mediates the survival of hematopoietic stem and progenitor cells in zebrafish