AUTHOR=Wang Yiming , Wu Hao , Jiang Xiangxiang , Jia Lei , Wang Meijiao , Rong Yin , Chen Shuo , Wang Yue , Xiao Zhenyu , Liang Xiaoyan , Wang Hongmei TITLE=LMNA Determines Nuclear Morphology During Syncytialization of Human Trophoblast Stem Cells JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.836390 DOI=10.3389/fcell.2022.836390 ISSN=2296-634X ABSTRACT=

Upon implantation, the trophectoderm differentiates into the multi-nucleated primitive syncytiotrophoblast (pSTB) through a process called primary syncytialization to facilitate maternal-fetal interactions and to establish a pregnancy. However, ethical issues and limited access to human embryos around the time of embryo implantation hinder the investigation of the detailed molecular mechanisms underpinning this event in humans. Here we established human trophoblast stem cells (hTSCs) from human blastocysts. We characterized nuclear enlargement in STB differentiated from hTSCs, which recapitulate morphological nuclear features of pSTB in human embryos. Specifically, we revealed that CRISPR/Cas9-mediated LMNA disruption perturbated nuclear volume during hTSCs syncytialization. Overall, our results not only provide an interesting insight into mechanisms underlying nuclear enlargement during primary syncytialization but highlight the hTSCs as an indispensable model in understanding human trophoblast differentiation during implantation.