Direct regulation of p53 by miR-142a-3p mediates the survival of hematopoietic stem and progenitor cells in zebrafish
- Lu, X., Wei, Y., Liu, F.
- Cell discovery 1: 15027 (Journal)
- Registered Authors
- Liu, Feng, Lu, Xinyan, Wei, Yonglong
- HSCs, HSPCs, miR-142a-3p, p53, survival, Haematopoietic stem cells
- MeSH Terms
- 27462426 Full text @ Cell Discov
Lu, X., Wei, Y., Liu, F. (2015) Direct regulation of p53 by miR-142a-3p mediates the survival of hematopoietic stem and progenitor cells in zebrafish. Cell discovery. 1:15027.
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.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes