生物钟在人类细胞的增殖和分化中起重要的作用，但人类胚胎干细胞体外分化过程中节律的建立及其对分化的影响尚不清楚。BMAL1是核心钟基因，在m6A mRNA甲基化作用下参与调控细胞周期和振荡的稳定性。本研究拟采用国际认可的人胚胎干细胞系H1为研究材料，建立生物钟核心基因BMAL1及钟控基因p21启动子的荧光素酶报告的H1细胞系，以及BMAL1敲减、敲除和过表达的H1细胞系模型，通过对比分析胚胎干细胞的自主分化和神经前体细胞的定向分化过程中WNT调控通路的作用以及m6A甲基化的表遗传修饰，探讨生物钟节律的产生及其对干细胞的增殖及分化的调控，从而为定向诱导分化提供新评估参数，促进人类胚胎干细胞在再生医学的临床应用。

Circadian clock plays an important role during the proliferation and differentiation of various human cells. However, the developmental process of cellular circadian oscillator formation during the differentiation of embryonic stem cells remains unknown. BMAL1 is one of the core circadian genes, which was found to be essential for the maintenance of circadian period and oscillation stability under the m6A mRNA methylation process. Here, we aim to compare the difference between autonomous and directional differentiation process, using knock down, knock out and over-expression BMAL1 hES cells, and BMAL1 and clock controlled gene p21 promoter-driven luciferase reporter hES cells, for the purpose of detecting the development of biological rhythms in hES cells, and more importantly, elucidating the WNT pathway of regulation of biological rhythms on hES cells proliferation and differentiation, and the role of m6A mRNA methylation process, thus to promote the clinical application of hES cells in regenerative medicine.