TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss

Proceedings of the National Academy of Sciences of the United States of America
Biswarup SahaSoumen Paul

Abstract

Early pregnancy loss affects ∼15% of all implantation-confirmed human conceptions. However, evolutionarily conserved molecular mechanisms that regulate self-renewal of trophoblast progenitors and their association with early pregnancy loss are poorly understood. Here, we provide evidence that transcription factor TEAD4 ensures survival of postimplantation mouse and human embryos by controlling self-renewal and stemness of trophoblast progenitors within the placenta primordium. In an early postimplantation mouse embryo, TEAD4 is selectively expressed in trophoblast stem cell-like progenitor cells (TSPCs), and loss of Tead4 in postimplantation mouse TSPCs impairs their self-renewal, leading to embryonic lethality before embryonic day 9.0, a developmental stage equivalent to the first trimester of human gestation. Both TEAD4 and its cofactor, yes-associated protein 1 (YAP1), are specifically expressed in cytotrophoblast (CTB) progenitors of a first-trimester human placenta. We also show that a subset of unexplained recurrent pregnancy losses (idiopathic RPLs) is associated with impaired TEAD4 expression in CTB progenitors. Furthermore, by establishing idiopathic RPL patient-specific human trophoblast stem cells (RPL-TSCs), we show...Continue Reading

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Citations

Aug 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Francesca Soncin, Mana M Parast
Feb 9, 2021·The Journal of Biological Chemistry·Adam MischlerBalaji M Rao
Feb 15, 2021·Cellular and Molecular Life Sciences : CMLS·Lucy LeBlancJonghwan Kim
Apr 13, 2021·Molecular Reproduction and Development·Mariagrazia PaonessaGiovanni Coticchio
Jun 15, 2021·Human Reproduction Update·John D Aplin, Carolyn J P Jones
Jun 16, 2021·Development·Laura CurreyMichael Piper
Jul 4, 2021·Tissue & Cell·Carlo TicconiAsgerally Fazleabas
Sep 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ruth HornbachnerPaulina A Latos
Oct 16, 2021·Development·Megan A SheridanMargherita Y Turco
Oct 16, 2021·BJOG : an International Journal of Obstetrics and Gynaecology·E R Barrozo, K M Aagaard

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