THAP1 is a master regulator of zinc finger transcription factors guiding gastrulation of murine embryos [RNA-seq_mESC]

Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo. Overall design: THAP1, ZFP764, ZFP524, and Zscan10 knock-out mESCs were generated and RNA-seq was performed to analyze gene expression changes in each cell line.

原肠胚形成（gastrulation）与早期器官发生（early organogenesis）是早期胚胎发育过程中极具标志性的生命进程。我们此前的研究表明，敲除DYT6基因（DYT6 gene）的编码产物THAP1，会导致胚胎在原肠胚形成及早期器官发生阶段致死。然而，THAP1在基因表达调控中的功能，以及其在胚胎原肠胚形成与早期器官发生过程中的作用，目前尚未得到充分阐明。本研究采用多种体外（in vitro）与体内（in vivo）模型，对THAP1在基因表达调控及胚胎发育调控中的功能进行系统解析；该研究不仅有助于我们理解THAP1相关疾病的发病机制，还可为小鼠胚胎原肠胚形成的转录调控机制研究提供数据支撑。实验设计概述：成功构建了THAP1、ZFP764、ZFP524及Zscan10基因敲除的小鼠胚胎干细胞（mouse embryonic stem cells, mESCs）模型，并通过RNA测序（RNA-seq）分析各细胞系中的基因表达变化。