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Publication : Nr5a2 ensures inner cell mass formation in mouse blastocyst.

First Author  Zhao Y Year  2024
Journal  Cell Rep Volume  43
Issue  3 Pages  113840
PubMed ID  38386558 Mgi Jnum  J:346140
Mgi Id  MGI:7613925 Doi  10.1016/j.celrep.2024.113840
Citation  Zhao Y, et al. (2024) Nr5a2 ensures inner cell mass formation in mouse blastocyst. Cell Rep 43(3):113840
abstractText  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.
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