抑制MTM1表达促进胚胎干细胞分化

应用随机RNAi文库，筛选了与胚胎干细胞自我更新和分化调控相关基因，发现了多个阳性候选基因，对其中的1个阳性候选基因肌管素1（myotubularin, MTM1）基因进行了深入研究．MTM1是属于蛋白酪氨酸磷酸酶（PTPase）蛋白家族的蛋白，其基因突变导致肌管性肌病．MTM1在胚胎干细胞中的功能到目前为止还不清楚．研究证实，MTM1在小鼠胚胎干细胞系CCE和R1均有表达．应用RNA干扰及集落形成实验证明，MTM1表达抑制后，处于自我更新状况胚胎干细胞集落的比例显著增加，提示MTM1在胚胎干细胞自我更新和分化的调控中起了重要的作用．

Knockdown of MTM1 Expression Promotes Differentiation of Embryonic Stem Cells

Myotubularin 1 (MTM1) belongs to a protein tyrosine phosphatase (PTPase) superfamily. Mutations in MTM1 lead to myotubular myopathy, an X-linked genetic muscular disorder. The exact function of MTM1 in embryonic stem cells remained unclear. A functional genetic screen of genes that regulate the self- renewal and the differentiation of embryonic stem cells were performed using a random RNA interference library. MTM1 was expressed and positively identified as a candidate gene in several stem cell lines, such as CCE and R1, The knockdown of MTM1 expression led to a significant decreased ratio of undifferentiated stem cell colonies as determined by colony forming experiments. Our results suggested that MTM1 might play an important role in the regulation of self renewal and differentiation in embryonic stem cells.