Sox2影响鸡胚胎生殖细胞神经系定向分化的表观遗传机制

Directed differentiation of embryonic stem cells (ES) into varieties of neural precursor cells and mature neural cells provides a good model for the elucidation of neural development in vitro. As a source of ES, embryonic germ cells (EG) have similar characteristic. Our previous studies demonstrated that chick EG can also directedly differentiate into neural lineage. Because Sox2 is not only one of the pluripotency-related genes, but also a marker for neural development, its dynamic expression pattern provides an excellent model to investigate the neural differentiation of ES. However, there is yet no report about the epigenetic change of Sox2 in the directed differentiation of chicken EG into neural lineage to date. Based on our previous works, we attempt to demonstrate the effect of Sox2 on the neural differentiation of chick EG. Subsequently, the aims of this study are: 1) to explore DNA methylation changes of Sox2 regulatory sequences and related mechanisms in neural differentiation of chick EG; 2) to study H3, H4 acetylation statuses of Sox2 regulatory sequences in neural differentiation of chick EG; 3) to observe the effect of specific inhibitor (alone and combined) on the neural differentiation of chick EG. In summary, this study aims to reveal the effect and the molecular mechanisms of epigenetic changes of Sox2 on the process of neural differentiation of chick EG.

将胚胎干细胞(ES)定向分化为各种神经前体细胞和神经细胞，为研究神经发育机制提供了良好的体外模型。胚胎生殖细胞（EG）作为ES的来源之一，具有与ES相似的特性，我们的前期工作证明，鸡EG同样可发生神经系定向分化。Sox2既是全能性相关基因，同时又是神经发育的标记，呈现动态表达模式，因此是研究ES神经系定向分化的极佳模型，然而其表观遗传改变在鸡EG神经系定向分化中的作用机制尚无报道。本课题拟在前期工作基础上，以Sox2为切入点，以鸡EG的神经分化为体外模型，1)探讨神经系定向分化不同阶段Sox2调控序列DNA甲基化的改变情况及相关机制；2)研究神经系定向分化不同阶段Sox2调控序列组蛋白H3、H4乙酰化改变的特点；3)观察特异性抑制剂单独（联合）应用后对鸡EG神经系定向分化过程的影响。本研究旨在从正反两个方面揭示Sox2表观遗传改变对鸡EG神经系分化进程的影响，并初步阐明相关的分子机制。

来源于原始生殖细胞的胚胎生殖细胞（EG），是胚胎干细胞（ES）的材料来源之一，EG定向分化为各种神经前体细胞和神经细胞，为研究神经发育机制提供了良好的体外模型。Sox2是维持干细胞全能性最主要的内源性调节因子，Sox2既是全能性相关基因，同时又是神经发育的标记，呈现动态表达模式，因此是研究EG神经系定向分化的极佳模型，然而其表观遗传改变在鸡EG神经系定向分化中的作用机制尚无报道。本课题在前期工作基础上，以Sox2为切入点，以鸡EG的神经分化为体外模型，从正反两个方面揭示了Sox2表观遗传改变对鸡EG神经系分化进程的影响，并初步阐明了相关的分子机制。1)探讨了神经系定向分化不同阶段Sox2调控序列DNA甲基化的改变情况及相关机制；2)研究神经系定向分化不同阶段Sox2调控序列组蛋白H3、H4乙酰化改变的特点；3)观察特异性抑制剂单独（联合）应用后对鸡EG神经系定向分化过程的影响。