气候变化领域集成服务门户(CCPortal): ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development

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DOI	10.1073/pnas.2016517118
	ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development
	Varberg K.M.; Iqbal K.; Muto M.; Simon M.E.; Scott R.L.; Kozai K.; Choudhury R.H.; Aplin J.D.; Biswell R.; Gibson M.; Okae H.; Arima T.; Vivian J.L.; Grundberg E.; Soares M.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast cell invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in mice identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development. We hypothesized that ASCL2 is a critical and conserved regulator of invasive trophoblast cell lineage development. In contrast to the mouse, the rat possesses deep intrauterine trophoblast cell invasion and spiral artery remodeling similar to human placentation. In this study, we investigated invasive/extravillous trophoblast (EVT) cell differentiation using human trophoblast stem (TS) cells and a loss-of-function mutant Ascl2 rat model. ASCL2 transcripts are expressed in the EVT column and junctional zone, which represent tissue sources of invasive trophoblast progenitor cells within human and rat placentation sites, respectively. Differentiation of human TS cells into EVT cells resulted in significant up-regulation of ASCL2 and several other transcripts indicative of EVT cell differentiation. Disruption of ASCL2 impaired EVT cell differentiation, as indicated by cell morphology and transcript profiles. RNA sequencing analysis of ASCL2-deficient trophoblast cells identified both down-regulation of EVT cell-associated transcripts and up-regulation of syncytiotrophoblast-associated transcripts, indicative of dual activating and repressing functions. ASCL2 deficiency in the rat impacted placental morphogenesis, resulting in junctional zone dysgenesis and failed intrauterine trophoblast cell invasion. ASCL2 acts as a critical and conserved regulator of invasive trophoblast cell lineage development and a modulator of the syncytiotrophoblast lineage. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Differentiation; Invasion; Placenta; Trophoblast
语种	英语
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/180391
作者单位	Institute for Reproduction and Perinatal Research, University of Kansas Medical Center, Kansas City, KS 66160, United States; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States; Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester, M13 9WL, United Kingdom; Academic Health Science Centre, St Mary’s Hospital, Manchester, M13 9WL, United Kingdom; Center for Pediatric Genomic Medicine, Children’s Mercy Research Institute, Kansas City, MO 64108, United States; Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan; Center for Perinatal Research, Children’s Mercy Research Institute, Kansas City, MO 64108, United States; Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, United States; Department of Obstetrics and Gynecology, University of Kansas Med...
推荐引用方式 GB/T 7714	Varberg K.M.,Iqbal K.,Muto M.,et al. ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development[J],2021,118(10).
APA	Varberg K.M..,Iqbal K..,Muto M..,Simon M.E..,Scott R.L..,...&Soares M.J..(2021).ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Varberg K.M.,et al."ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).