ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development
ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development
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ASCL2在血绒质胎盘发育过程中相互控制关键的滋养层谱系决策
DOI：
10.1073/pnas.2016517118
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Soares Michael J.
中科院分区：
文献类型：
--
作者：
Varberg Kaela M.;Iqbal Khursheed;Muto Masanaga;Simon Mikaela E.;Scott Regan L.;Kozai Keisuke;Choudhury Ruhul H.;Aplin John D.;Biswell Rebecca;Gibson Margaret;Okae Hiroaki;Arima Takahiro;Vivian Jay L.;Grundberg Elin;Soares Michael J.
侵袭性滋养层细胞在血绒膜胎盘形成中对螺旋动脉重塑至关重要。滋养层细胞浸润不足和血管重塑可导致妊娠障碍，包括先兆子痫、早产和子宫内生长受限。先前在小鼠中的研究确定无毛鳞片同源物2（ASCL2）是胚外发育所必需的。我们假设ASCL2是浸润性滋养层细胞谱系发育的关键和保守的调节因子。与小鼠相反，大鼠具有类似于人类胎盘的子宫内滋养层细胞浸润和螺旋动脉重塑。本研究利用人滋养层干细胞（TS）和功能缺失的小鼠Ascl2大鼠模型研究了侵袭性/绒毛外滋养层（EVT）细胞的分化，发现ASCL2转录本在EVT柱和交界区表达，这两个区域分别代表人和大鼠胎盘形成部位侵袭性滋养层祖细胞的组织来源。人TS细胞向EVT细胞分化导致ASCL2和其他几种指示EVT细胞分化的转录物显著上调。ASCL2的破坏损害EVT细胞分化，如细胞形态和转录谱所示。ASCL2缺陷滋养层细胞的RNA测序分析确定了EVT细胞相关转录物的下调和合胞体滋养层相关转录物的上调，表明双重激活和抑制功能。大鼠ASCL2缺陷影响胎盘形态发生，导致结合区发育不全和子宫内滋养层细胞浸润失败。ASCL2作为侵入性滋养层细胞谱系发育的关键和保守的调节剂和合体滋养层谱系的调节剂。
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 mutantAscl2rat model.ASCL2transcripts 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 ofASCL2and 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.
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影响因子：
3.8
作者：
M. Soares;B. M. Chapman;C. Rasmussen;G. Dai;T. Kamei;K. Orwig
通讯作者：
M. Soares;B. M. Chapman;C. Rasmussen;G. Dai;T. Kamei;K. Orwig
破坏远端小鼠 7 号染色体印记结构域的截断的表观遗传和表型后果
影响因子：
5.3
作者：
R. Oh;Rita Ho;L. Mar;M. Gertsenstein;J. Paděrová;J. Hsien;J. Squire;M. Higgins;A. Nagy;L. Lefebvre
通讯作者：
L. Lefebvre
影响因子：
10.4
作者：
Dorgan JF;Longcope C;Stephenson HE Jr;Falk RT;Miller R;Franz C;Kahle L;Campbell WS;Tangrea JA;Schatzkin A
通讯作者：
Schatzkin A
大鼠胎盘的表型分析。
DOI：
10.1385/1-59259-983-4:293
发表时间：
2006
期刊：
Methods in molecular medicine
影响因子：
--
作者：
Ain,Rupasri;Konno,Toshihiro;Canham,LindseyN;Soares,MichaelJ
通讯作者：
Soares,MichaelJ
影响因子：
5.9
作者：
Cinkornpumin, Jessica K.;Kwon, Sin Young;Pastor, William A.
通讯作者：
Pastor, William A.