Table_4_C1EIP Functions as an Activator of ENO1 to Promote Chicken PGCs Formation via Inhibition of the Notch Signaling Pathway.docx

The production of germ cells, especially primordial germ cells (PGCs), is important for avian stem cells and reproduction biology. However, key factors involved in the regulation of PGCs remain unknown. Here, we report a PGC-related marker gene: C1EIP (Chromosome 1 Expression in PGCs), whose activation and expression are regulated by the transcription factor STAT3 (signal transducer and activator of transcription 3), histone acetylation, and promoter methylation. C1EIP regulates PGCs formation by mediating the expression of PGC-associated genes, such as CVH (Chicken Vasa Homologous) and CKIT (Chicken KIT proto-oncogene). C1EIP knockdown during embryonic development reduces PGC generation efficiency both in vitro and in ovo. Conversely, C1EIP overexpression increases the formation efficiency of PGCs. C1EIP encodes a cytoplasmic protein that interacts with ENO1 (Enolase 1) in the cytoplasm, inhibits the Notch signaling pathway, and positively regulates PGC generation. Collectively, our findings demonstrate C1EIP as a novel gene involved in PGC formation, which regulates genes involved in embryonic stem cell differentiation through interaction with ENO1 and subsequent inhibition of the Notch signaling pathway by the impression of Myc (MYC proto-oncogene).

胚胎干细胞的产生，尤其是原始生殖细胞（PGCs），对于鸟类的干细胞生物学和繁殖生物学至关重要。然而，调控PGCs的关键因素尚不明确。本研究报告了一种与PGCs相关的标记基因：C1EIP（染色体1在PGCs中的表达），其激活和表达受转录因子STAT3（信号转导和转录激活因子3）、组蛋白乙酰化和启动子甲基化的调控。C1EIP通过介导PGC相关基因的表达，如CVH（鸡Vasa同源基因）和CKIT（鸡KIT原癌基因）的表达，来调控PGCs的形成。在胚胎发育过程中，C1EIP的敲低降低了体外和体内PGC的产生效率。相反，C1EIP的过表达增加了PGCs的形成效率。C1EIP编码一种细胞质蛋白，该蛋白与细胞质中的ENO1（烯醇化酶1）相互作用，抑制Notch信号通路，并正向调控PGCs的形成。总之，我们的研究结果揭示了C1EIP作为一种参与PGCs形成的全新基因，它通过与ENO1相互作用，进而通过Myc（MYC原癌基因）的影响抑制Notch信号通路，从而调节参与胚胎干细胞分化的基因。