气候变化领域集成服务门户(CCPortal): TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss

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DOI	10.1073/pnas.2002449117
	TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss
	Saha B.; Ganguly A.; Home P.; Bhattacharya B.; Ray S.; Ghosh A.; Karim Rumi M.A.; Marsh C.; French V.A.; Gunewardena S.; Paul S.
发表日期	2020
ISSN	0027-8424
起始页码	17864
结束页码	17875
卷号	117 期号:30
英文摘要	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 that loss of TEAD4 is associated with defective self-renewal in RPL-TSCs and rescue of TEAD4 expression restores their self-renewal ability. Unbiased genomics studies revealed that TEAD4 directly regulates expression of key cell cycle genes in both mouse and human TSCs and establishes a conserved transcriptional program. Our findings show that TEAD4, an effector of the Hippo signaling pathway, is essential for the establishment of pregnancy in a postimplantation mammalian embryo and indicate that impairment of the Hippo signaling pathway could be a molecular cause for early human pregnancy loss. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Hippo signaling; Placenta; Recurrent pregnancy loss; TEAD4; Trophoblast progenitor
语种	英语
scopus关键词	TEAD4 protein; transcription factor; unclassified drug; biological marker; DNA binding protein; muscle protein; TEAD4 protein, human; transcription factor; animal cell; animal experiment; Article; cell cycle; cell self-renewal; controlled study; cytotrophoblast; embryo; embryo death; embryo development; female; first trimester pregnancy; gene expression regulation; genetic transcription; hippo signaling; human; human cell; human tissue; mouse; nidation; nonhuman; priority journal; protein expression; recurrent pregnancy loss; spontaneous abortion; stem cell; trophoblast; trophoblast stem cell; animal; cell self-renewal; cytology; disease model; disease predisposition; embryo development; fluorescent antibody technique; genetics; immunohistochemistry; metabolism; nidation; placenta; pregnancy; recurrent abortion; spontaneous abortion; trophoblast; Abortion, Habitual; Abortion, Spontaneous; Animals; Biomarkers; Cell Self Renewal; Disease Models, Animal; Disease Susceptibility; DNA-Binding Proteins; Embryo Implantation; Embryonic Development; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Developmental; Humans; Immunohistochemistry; Mice; Muscle Proteins; Placenta; Pregnancy; Transcription Factors; Trophoblasts
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160253
作者单位	Saha, B., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States; Ganguly, A., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States; Home, P., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States, Institute for Reproduction and Perinatal Research, University of Kansas Medical Center, Kansas City, KS 66160, United States; Bhattacharya, B., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States; Ray, S., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States; Ghosh, A., Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States; Karim Rumi, M.A., Department of Pathology and Laboratory Medicine, Unive...
推荐引用方式 GB/T 7714	Saha B.,Ganguly A.,Home P.,et al. TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss[J],2020,117(30).
APA	Saha B..,Ganguly A..,Home P..,Bhattacharya B..,Ray S..,...&Paul S..(2020).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,117(30).
MLA	Saha B.,et al."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 117.30(2020).