Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, 75015 Paris, France.
Sorbonne Université, Complexité du Vivant, 75005 Paris, France.
Science. 2024 Oct 4;386(6717):eadg7325. doi: 10.1126/science.adg7325.
Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify the lineages constituting the blastocyst. Although the TFs specifying the blastocyst's lineages are well characterized, those playing earlier roles remain poorly defined. Using mouse models of the TF , we show that embryos arrest at the early morula stage and exhibit altered lineage specification, frequent mitotic failure, and substantial chromosome segregation defects. Although NR5A2 plays a minor but measurable role during zygotic genome activation, it predominantly acts as a master regulator at the eight-cell stage, controlling expression of lineage-specifying TFs and genes involved in mitosis, telomere maintenance, and DNA repair. We conclude that NR5A2 coordinates proliferation, genome stability, and lineage specification to ensure correct morula development.
早期胚胎发生由转录因子(TFs)驱动,这些因子首先激活合子基因组,然后指定构成囊胚的谱系。尽管指定囊胚谱系的 TFs 已经得到很好的描述,但那些更早发挥作用的 TFs 仍然定义不明确。我们使用 TF 的小鼠模型表明,NR5A2 缺失的胚胎在早期桑葚胚阶段停滞,并表现出谱系特异性改变、频繁的有丝分裂失败和大量的染色体分离缺陷。尽管 NR5A2 在合子基因组激活过程中发挥了次要但可测量的作用,但它主要作为一个主调控因子在八细胞阶段发挥作用,控制谱系特异性 TF 的表达以及参与有丝分裂、端粒维持和 DNA 修复的基因。我们得出结论,NR5A2 协调增殖、基因组稳定性和谱系特异性,以确保正确的桑葚胚发育。