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

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.