Suppression of GATA3 promotes epithelial-mesenchymal transition and simultaneous cellular senescence in human extravillous trophoblasts

作者全名：Chen, En-Xiang; Hu, Si-Chen; Xu, Jia-Qi; Liu, Kun-Yan; Tang, Jing; Shen, Xi-Peng; Liang, Xiao; Xie, You-Long; Ge, Lu-Xin; Luo, Xin; Wang, Ying-Xiong; Xiang, Yun-Long; Ding, Yu-Bin

作者地址：[Xiang, Yun-Long] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing 401147, Peoples R China; [Chen, En-Xiang; Xu, Jia-Qi; Tang, Jing; Shen, Xi-Peng; Liang, Xiao] Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Chongqing 400016, Peoples R China; [Chen, En-Xiang; Hu, Si-Chen; Tang, Jing; Xie, You-Long; Ge, Lu-Xin; Wang, Ying-Xiong] Chongqing Med Univ, Sch Publ Hlth, Dept Toxicol, Joint Int Res Lab Reprod & Dev Minist Educ China, Chongqing 400016, Peoples R China; [Luo, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing, Peoples R China; [Chen, En-Xiang] Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Dept Basic Med Sci, Changsha 410219, Hunan, Peoples R China; [Ge, Lu-Xin] Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Hunan, Peoples R China; [Wang, Ying-Xiong; Xiang, Yun-Long; Ding, Yu-Bin] Chongqing Med Univ, Box 197, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China

通信作者：Wang, YX; Xiang, YL; Ding, YB (通讯作者)，Chongqing Med Univ, Box 197, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.

来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001251959800001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：1871

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：Extravillous trophoblasts; GATA3; Epithelial-mesenchymal transition; Cellular senescence; Cell migration

摘要：The regulatory mechanism of the transcription factor GATA3 in the differentiation and maturation process of extravillous trophoblasts (EVT) in early pregnancy placenta, as well as its relevance to the occurrence of pregnancy disorders, remains poorly understood. This study leveraged single-cell RNA sequencing data from placental organoid models and placental tissue to explore the dynamic changes in GATA3 expression during EVT maturation. The expression pattern exhibited an initial upregulation followed by subsequent downregulation, with aberrant GATA3 localization observed in cases of recurrent miscarriage (RM). By identifying global targets regulated by GATA3 in primary placental EVT cells, JEG3, and HTR8/SVneo cell lines, this study offered insights into its regulatory mechanisms across different EVT cell models. Shared regulatory targets among these cell types and activation of trophoblast cell marker genes emphasized the importance of GATA3 in EVT differentiation and maturation. Knockdown of GATA3 in JEG3 cells led to repression of GATA3-induced epithelial-mesenchymal transition (EMT), as evidenced by changes in marker gene expression levels and enhanced migration ability. Additionally, interference with GATA3 accelerated cellular senescence, as indicated by reduced proliferation rates and increased activity levels for senescence-associated beta-galactosidase enzyme, along with elevated expression levels for senescence-associated genes. This study provides comprehensive insights into the dual role of GATA3 in regulating EMT and cellular senescence during EVT differentiation, shedding light on the dynamic changes in GATA3 expression in normal and pathological placental conditions.

基金机构：National Natural Sci-ence Foundation of China [82101762, 82171664, 32270636]; Natural Science Foundation Project of Chongqing [cstc2021jcyj-bshX0122, CSTB2022NSCQ-LZX0062]

基金资助正文：This study was supported by grants from the National Natural Sci-ence Foundation of China (Nos. 82101762, 82171664, 32270636) and the Natural Science Foundation Project of Chongqing (Nos. cstc2021jcyj-bshX0122, CSTB2022NSCQ-LZX0062) .