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PHD2 safeguards modest mesendoderm development.
- Source :
-
Communications biology [Commun Biol] 2024 Sep 07; Vol. 7 (1), pp. 1100. Date of Electronic Publication: 2024 Sep 07. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Mesoderm metabolism
Mesoderm embryology
Gene Expression Regulation, Developmental
Wnt Signaling Pathway
Endoderm metabolism
Endoderm embryology
MicroRNAs metabolism
MicroRNAs genetics
Hypoxia-Inducible Factor-Proline Dioxygenases metabolism
Hypoxia-Inducible Factor-Proline Dioxygenases genetics
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 39244636
- Full Text :
- https://doi.org/10.1038/s42003-024-06824-z