Publication Date
7-9-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2404062121
PMID
38968109
PMCID
PMC11253012
PubMedCentral® Posted Date
7-5-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Trophoblasts, Humans, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Female, Pregnancy, Mice, Animals, Cell Differentiation, Mechanistic Target of Rapamycin Complex 1, Placenta, Signal Transduction, Autophagy, syncytiotrophoblast, TFEB, ERVFRD-1, human trophoblast stem cell, fetal growth restriction
Abstract
The formation of multinucleated syncytiotrophoblast (STB) through cell fusion of cytotrophoblast, also termed syncytialization, ensures the proper placental structure and functions. Nutrient insufficiency and inactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in trophoblasts have been shown to enhance STB formation; however, the underlying mechanism remains elusive. Here, we showed that the deficiency of a mTORC1 downstream transcriptional factor, TFEB, significantly impaired STB formation in human trophoblasts and knock-out mice. TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 and thereby promoted trophoblast syncytialization. Additionally, TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth restriction placentas with suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis safeguards proper STB formation during placenta development.
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Allergy and Immunology Commons, Immune System Diseases Commons, Medical Immunology Commons
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