Table_5_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).

胚细胞的生成，尤其是原始生殖细胞（PGCs），对于鸟类干细胞及其繁殖生物学具有重要意义。然而，参与PGCs调控的关键因素尚不清楚。在本研究中，我们报道了一种与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通过介导与PGCs相关的基因，如CVH（鸡Vasa同源）和CKIT（鸡KIT原癌基因）的表达，调控PGCs的形成。在胚胎发育过程中，C1EIP敲低降低了体外和体内PGCs的生成效率。相反，C1EIP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的生成。总之，我们的研究结果表明，C1EIP是一种参与PGCs形成的全新基因，它通过与ENO1的相互作用调节参与胚胎干细胞分化的基因，并通过Myc（MYC原癌基因）的诱导抑制Notch信号通路。