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Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):E6175-84. doi: 10.1073/pnas.1507397112. Epub 2015 Oct 26.

OVO-like 1 regulates progenitor cell fate in human trophoblast development.

Author information

1
Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160; srenaud4@uwo.ca msoares@kumc.edu.
2
Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160;
3
Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160; Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160.
4
Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160; Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160 srenaud4@uwo.ca msoares@kumc.edu.

Abstract

Epithelial barrier integrity is dependent on progenitor cells that either divide to replenish themselves or differentiate into a specialized epithelium. This paradigm exists in human placenta, where cytotrophoblast cells either propagate or undergo a unique differentiation program: fusion into an overlying syncytiotrophoblast. Syncytiotrophoblast is the primary barrier regulating the exchange of nutrients and gases between maternal and fetal blood and is the principal site for synthesizing hormones vital for human pregnancy. How trophoblast cells regulate their differentiation into a syncytium is not well understood. In this study, we show that the transcription factor OVO-like 1 (OVOL1), a homolog of Drosophila ovo, regulates the transition from progenitor to differentiated trophoblast cells. OVOL1 is expressed in human placenta and was robustly induced following stimulation of trophoblast differentiation. Disruption of OVOL1 abrogated cytotrophoblast fusion and inhibited the expression of a broad set of genes required for trophoblast cell fusion and hormonogenesis. OVOL1 was required to suppress genes that maintain cytotrophoblast cells in a progenitor state, including MYC, ID1, TP63, and ASCL2, and bound specifically to regions upstream of each of these genes. Our results reveal an important function of OVOL1 as a regulator of trophoblast progenitor cell fate during human trophoblast development.

KEYWORDS:

OVO-like 1; differentiation; epithelial barrier; placenta; trophoblast

PMID:
26504231
PMCID:
PMC4653227
DOI:
10.1073/pnas.1507397112
[Indexed for MEDLINE]
Free PMC Article

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