动态尾部型同源盒2表达对植入过程中人滋养层谱系分化的影响。
The impact of dynamic caudal type homeobox 2 expression on the differentiation of human trophoblast lineage during implantation.
发表日期：2024 Aug 19
作者：
Lujuan Rong, Lifeng Xiang, Zongyong Ai, Baohua Niu, Yaqing Wang, Yu Yin, Chun Feng, Gaohui Shi, Tingwei Chen, Jie Yang, Xi Luo, Yun Bai, Xiaoting Zhou, Xiaoping Liu, Haishan Zheng, Yang Ke, Tianqing Li, Ze Wu
来源：
CELL PROLIFERATION
摘要：
滋养层谱系分化是成功胚胎植入的限速步骤。滋养层内的粘附、侵袭和迁移过程由多种转录因子控制。其中，CDX2是塑造滋养层命运的关键调节因子。虽然其表达改变是启动小鼠胚胎植入的关键，但 CDX2 对早期人类滋养层功能和谱系分化的精确影响仍不清楚。在这项研究中，我们采用了成熟的 CDX2 过表达人类滋养层干细胞 (hTSC) 系以及早期人类胚胎的 3D 体外培养系统。基于免疫荧光、转录组分析、CUT 标签测序和 3D 人类滋养层类器官的构建，我们发现 CDX2 的下调是人类胚胎植入过程中合胞化的先决条件。虽然 CDX2 过表达抑制合胞化，但它促进 hTSC 增殖和侵袭性迁移。 CDX2通过与CGA、PTGS2、GCM1、LEF1和CDH2相互作用发挥影响，从而阻碍合体滋养层的过早分化。 CDX2 过表达增强了人滋养层类器官的上皮-间质转化。总之，我们的研究深入了解了人类滋养层分化和发育的分子特征，为推进胚胎植入研究奠定了理论基础。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》
The trophoblast lineage differentiation represents a rate-limiting step in successful embryo implantation. Adhesion, invasion and migration processes within the trophoblast are governed by several transcription factors. Among them, CDX2 is a critical regulator shaping the destiny of the trophoblast. While its altered expression is a linchpin initiating embryo implantation in mice, the precise influence of CDX2 on the functionality and lineage differentiation of early human trophoblast remains unclear. In this study, we employed well-established human trophoblast stem cell (hTSC) lines with CDX2 overexpression coupled with a 3D in vitro culture system for early human embryos. We revealed that the downregulation of CDX2 is a prerequisite for syncytialization during human embryo implantation based on immunofluorescence, transcriptome analysis, CUT-tag sequencing and the construction of 3D human trophoblast organoids. While CDX2 overexpression inhibited syncytialization, it propelled hTSC proliferation and invasive migration. CDX2 exerted its influence by interacting with CGA, PTGS2, GCM1, LEF1 and CDH2, thereby hindering premature differentiation of the syncytiotrophoblast. CDX2 overexpression enhanced the epithelial-mesenchymal transition of human trophoblast organoids. In summary, our study provides insights into the molecular characteristics of trophoblast differentiation and development in humans, laying a theoretical foundation for advancing research in embryo implantation.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.