First Author | Li M | Year | 2024 |
Journal | Commun Biol | Volume | 7 |
Issue | 1 | Pages | 1100 |
PubMed ID | 39244636 | Mgi Jnum | J:354214 |
Mgi Id | MGI:7731347 | Doi | 10.1038/s42003-024-06824-z |
Citation | Li M, et al. (2024) PHD2 safeguards modest mesendoderm development. Commun Biol 7(1):1100 |
abstractText | PHD2 is essential in modulating HIF-1alpha levels upon oxygen fluctuations. Hypoxia, a hallmark of uterus, and HIF-1alpha 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-1alpha. 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-1alpha regulated Wnt/beta-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-1alpha. |