Wdr82调控小鼠胚胎干细胞体外的增殖和分化  

Wdr82 Regulates the Proliferation and Differentiation of mESCs

作　　者：张薇 刘露露 惠心慧 万晓玲 周培培 张岩[2] 陈红霞[1] Zhang Wei;Liu Lulu;Hui Xinhui;Wan Xiaoling;Zhou Peipei;Zhang Yan;Chen Hongxia(School of Life Sciences,Shanghai University,Shanghai 200444,China;Institut Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai 200031,China)

机构地区：[1]上海大学生命科学学院,上海200444 [2]中国科学院上海巴斯德研究所,上海200031

出　　处：《中国细胞生物学学报》2018年第8期1312-1318,共7页Chinese Journal of Cell Biology

基　　金：国家自然科学基金项目(批准号:31670906;31471207)资助的课题~~

摘　　要：Setd1a复合物和Setd1b复合物(Setd1a/b)是进化上功能高度保守的表观遗传调控因子,主要包括Setd1a/b、Wdr82、Wdr5、Rbbp5、Ash2L、Dpy-30、Hcf-1等,催化组蛋白H3第4位赖氨酸(H3K4)的甲基化,进而激活基因转录。Wdr82是Setd1a/b复合物中特有的非催化亚基,其在胚胎发育过程中的作用尚不清楚。该研究利用小鼠胚胎干细胞(moue embryonic stem cells,m ESCs)的体外培养和分化系统发现,在m ESCs分化过程中,Wdr82的表达水平显著降低。在m ESCs中敲低Wdr82后,m ESCs的增殖速度显著减缓,而其多能性不受影响。利用拟胚体分化体系发现,Wdr82敲低后,拟胚体的形成速度变慢,自主搏动的时间明显滞后。综上所述,该结果揭示了Wdr82在m ESCs体外增殖和分化过程中的重要作用。Setd1 a complex and Setd1 b complex（Setd1 a/b） are evolutionarily conserved histone-modifying enzymes that play critical roles in transcriptional activation by promoting methylation of histone H3 on Lysine 4（H3 K4）. Setd1 a/b complex includes Setd1 a/b, Wdr82, Wdr5, Rbbp5, Ash2 L, Dpy-30, Hcf-1. Wdr82 is a conserved non-catalytic subunit of Setd1 a/b complex, however, the role of the Wdr82 during embryonic stem cells differentiation remains poorly understood. In this study, by moue embryonic stem cells（m ESCs） cell culture and differentiation in vitro system, we found that Wdr82 m RNA level was decreased during m ESCs differentiation. Wdr82 knockdown inhibited proliferation but not pluripotency of m ESCs. Wdr82 knockdown slowed down embryoid body formation rate and contractile activity. Therefore, our results uncovered a vital role of Wdr82 in m ESCs proliferation and differentiation.

关 键 词：Wdr82 小鼠胚胎干细胞 细胞增殖 细胞分化 多能性 

分 类 号：Q344[生物学—遗传学]