气候变化领域集成服务门户(CCPortal): Atypical protein kinase C iota (PKC?/?) ensures mammalian development by establishing the maternal-fetal exchange interface

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DOI	10.1073/pnas.1920201117
	Atypical protein kinase C iota (PKC?/?) ensures mammalian development by establishing the maternal-fetal exchange interface
	Bhattacharya B.; Home P.; Home P.; Ganguly A.; Ray S.; Ghosh A.; Islam M.R.; French V.; French V.; Marsh C.; Marsh C.; Gunewardena S.; Okae H.; Arima T.; Paul S.; Paul S.; Paul S.
发表日期	2020
ISSN	0027-8424
起始页码	14280
结束页码	14291
卷号	117 期号:25
英文摘要	In utero mammalian development relies on the establishment of the maternal-fetal exchange interface, which ensures transportation of nutrients and gases between the mother and the fetus. This exchange interface is established via development of multinucleated syncytiotrophoblast cells (SynTs) during placentation. In mice, SynTs develop via differentiation of the trophoblast stem cell-like progenitor cells (TSPCs) of the placenta primordium, and in humans, SynTs are developed via differentiation of villous cytotrophoblast (CTB) progenitors. Despite the critical need in pregnancy progression, conserved signaling mechanisms that ensure SynT development are poorly understood. Herein, we show that atypical protein kinase C iota (PKCγ/ι) plays an essential role in establishing the SynT differentiation program in trophoblast progenitors. Loss of PKCγ/ι in the mouse TSPCs abrogates SynT development, leading to embryonic death at approximately embryonic day 9.0 (E9.0).We also show that PKCγ/ι-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. PKCγ/ι is selectively expressed in the first-trimester CTBs of a developing human placenta. Furthermore, loss of PKCγ/ι in CTB-derived human trophoblast stem cells (human TSCs) impairs their SynT differentiation potential both in vitro and after transplantation in immunocompromised mice. Our mechanistic analyses indicate that PKCγ/ι signaling maintains expression of GCM1, GATA2, and PPARγ, which are key transcription factors to instigate SynT differentiation programs in both mouse and human trophoblast progenitors. Our study uncovers a conserved molecular mechanism, in which PKCγ/ι signaling regulates establishment of the maternal-fetal exchange surface by promoting trophoblast progenitor-to-SynT transition during placentation. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Cytotrophoblast; Human trophoblast stem cell; Placenta; Protein kinase Cγ/ι; Syncytiotrophoblast
语种	英语
scopus关键词	peroxisome proliferator activated receptor gamma; protein kinase C iota; transcription factor; transcription factor GATA 2; transcription factor GCM1; unclassified drug; DNA binding protein; GATA2 protein, human; Gata2 protein, mouse; GCM1 protein, human; Gcm1 protein, mouse; isoenzyme; peroxisome proliferator activated receptor gamma; protein kinase C; protein kinase C lambda; transcription factor; transcription factor GATA 2; animal cell; animal tissue; Article; cell death; cell differentiation; cell maturation; controlled study; embryo; female; first trimester pregnancy; human; human cell; human tissue; in vitro study; mother fetus relationship; mouse; nonhuman; placenta development; priority journal; protein depletion; protein expression; protein function; signal transduction; stem cell; syncytiotrophoblast cell; transplantation; trophoblast; animal; animal model; cytology; fetomaternal transfusion; genetics; knockout mouse; male; metabolism; physiology; placenta; pregnancy; Animals; Cell Differentiation; DNA-Binding Proteins; Female; GATA2 Transcription Factor; Humans; Isoenzymes; Male; Maternal-Fetal Exchange; Mice; Mice, Knockout; Models, Animal; Placenta; Placentation; PPAR gamma; Pregnancy; Protein Kinase C; Signal Transduction; Stem Cells; 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/160284
作者单位	Bhattacharya, B., 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; 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; Ganguly, A., 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 ...
推荐引用方式 GB/T 7714	Bhattacharya B.,Home P.,Home P.,et al. Atypical protein kinase C iota (PKC?/?) ensures mammalian development by establishing the maternal-fetal exchange interface[J],2020,117(25).
APA	Bhattacharya B..,Home P..,Home P..,Ganguly A..,Ray S..,...&Paul S..(2020).Atypical protein kinase C iota (PKC?/?) ensures mammalian development by establishing the maternal-fetal exchange interface.Proceedings of the National Academy of Sciences of the United States of America,117(25).
MLA	Bhattacharya B.,et al."Atypical protein kinase C iota (PKC?/?) ensures mammalian development by establishing the maternal-fetal exchange interface".Proceedings of the National Academy of Sciences of the United States of America 117.25(2020).