Abstract：
Recent studies have elucidated Nr5a2\'s role in activating zygotic genes during early mouse embryonic development. Subsequent research, however, reveals that Nr5a2 is not critical for zygotic genome activation but is vital for the gene program between the 4- and 8-cell stages. A significant gap exists in experimental evidence regarding its function during the first lineage differentiation\'s pivotal period. In this study, we observed that approximately 20% of embryos developed to the blastocyst stage following Nr5a2 ablation. However, these blastocysts lacked inner cell mass (ICM), highlighting Nr5a2\'s importance in first lineage differentiation. Mechanistically, using RNA sequencing and CUT&Tag, we found that Nr5a2 transcriptionally regulates ICM-specific genes, such as Oct4, to establish the pluripotent network. Interference with or overexpression of Nr5a2 in single blastomeres of 2-cell embryos can alter the fate of daughter cells. Our results indicate that Nr5a2 works as a doorkeeper to ensure ICM formation in mouse blastocyst.
摘要：
最近的研究已经阐明了Nr5a2在小鼠早期胚胎发育过程中激活合子基因的作用。随后的研究，然而,揭示Nr5a2对于合子基因组激活不是关键的,但对于4-和8-细胞阶段之间的基因程序是至关重要的。在第一个谱系分化的关键时期，关于其功能的实验证据存在显着差距。在这项研究中,我们观察到大约20%的胚胎在Nr5a2消融后发育到囊胚期.然而,这些胚泡缺乏内细胞团（ICM），强调Nr5a2在第一谱系分化中的重要性。机械上,使用RNA测序和CUT&Tag，我们发现Nr5a2转录调节ICM特异性基因，如Oct4，建立多能网络。在2细胞胚胎的单个卵裂球中干扰或过度表达Nr5a2可以改变子细胞的命运。我们的结果表明，Nr5a2可以作为看门人来确保ICM在小鼠胚泡中的形成。
