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机构地区:[1]解放军总医院309临床部,北京100091 [2]第三军医大学微生物学教研室,重庆400038
出 处:《中国生物化学与分子生物学报》2008年第10期938-942,共5页Chinese Journal of Biochemistry and Molecular Biology
基 金:国家自然科学基金资助项目(No.30370603;30470094;30700418)~~
摘 要: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.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 ceils.
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