PHD2 safeguards modest mesendoderm development.

Autor: Li M; College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China., Jin H; College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China., Zhao Y; College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China., Zhu G; College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China., Liu Y; Department of Biology and Biochemistry, University of Houston, Houston, TX, USA., Long H; Institute of Evolution and Marine Biodiversity, KLMME, Ocean University of China, Qingdao, Shandong, China., Shen X; College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China. shenxiaopeng_cn@ahnu.edu.cn.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Sep 07; Vol. 7 (1), pp. 1100. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1038/s42003-024-06824-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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