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- Title
PHD2 safeguards modest mesendoderm development.
- Authors
Li, Meng; Jin, Huaizhang; Zhao, Yun; Zhu, Guoping; Liu, Yu; Long, Hongan; Shen, Xiaopeng
- Abstract
PHD2 is essential in modulating HIF-1α levels upon oxygen fluctuations. Hypoxia, a hallmark of uterus, and HIF-1α have recently emerged as opposing regulators of mesendoderm specification, suggesting a role for PHD2 therein. We found that PHD2 expression initially covered the epiblast and gradually receded from the primitive streak, which was identical to hypoxia and exclusive to HIF-1α. The investigations performed in mESCs, embryoids, and mouse embryos together demonstrated that PHD2 negatively regulated mesendoderm specification. Single-cell RNA sequencing revealed that PHD2 governed the transition from epiblast to mesendoderm. The downstream effect of PHD2 relied on the HIF-1α regulated Wnt/β-catenin pathway, while it was regulated upstream by miR-429. In summary, our research highlights PHD2’s essential role in mesendoderm specification and its interactions with hypoxia and HIF-1α.PHD2-mediated pseudohypoxia, rather than ambient hypoxia, safeguards a balanced mesendoderm specification, relying on the HIF1α-regulated Wnt/β-catenin pathway.
- Publication
Communications Biology, 2024, Vol 7, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-024-06824-z