2. Academic Validation
  3. Suppression of GATA3 promotes epithelial-mesenchymal transition and simultaneous cellular senescence in human extravillous trophoblasts

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

  • Biochim Biophys Acta Mol Cell Res. 2024 Jun 4;1871(7):119768. doi: 10.1016/j.bbamcr.2024.119768.
En-Xiang Chen 1,  Si-Chen Hu 2,  Jia-Qi Xu 2,  Kun-Yan Liu 3,  Jing Tang 4,  Xi-Peng Shen 3,  Xiao Liang 3,  You-Long Xie 2,  Lu-Xin Ge 5,  Xin Luo 6,  Ying-Xiong Wang 7,  Yun-Long Xiang 8,  Yu-Bin Ding 9
Affiliations

Affiliations

  • 1 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Department of Toxicology, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China; Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Department of Basic Medical Sciences, Changsha Medical University, Hunan 410219, China.
  • 2 Department of Toxicology, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China.
  • 3 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
  • 4 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Department of Toxicology, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China.
  • 5 Department of Toxicology, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China; Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University. Hunan 410219, China.
  • 6 Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 7 Department of Toxicology, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China. Electronic address: 100115@cqmu.edu.cn.
  • 8 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: xiangyl@cqmu.edu.cn.
  • 9 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing 401147, China; Department of Toxicology, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 400016, China. Electronic address: dingyb@cqmu.edu.cn.
PMID: 38838858 DOI: 10.1016/j.bbamcr.2024.119768
Abstract

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 β-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.

Keywords

Cell migration; Cellular senescence; Epithelial-mesenchymal transition; Extravillous trophoblasts; GATA3.

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