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抑制MTM1表达促进胚胎干细胞分化

Knockdown of MTM1 Expression Promotes Differentiation of Embryonic Stem Cells
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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.
作者 程小星 蹇锐
机构地区 解放军总医院 第三军医大学微生物学教研室
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 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)~~
关键词 肌管素1 胚胎干细胞 分化 自我更新 myotubularin 1 embryonic stem cells differentiation self-renewal
分类号 Q255 [生物学—细胞生物学]
  • 相关文献

参考文献15

  • 1Shackleton M, Vaillant F, Simpson K J, et al. Generation of a functional mammary gland from a single stem cell[J]. Nature, 2006, 439 (7072) : 84-88
  • 2Mitjavila-Garcia M T, Simonin C, Peschanski M. Embryonic stem cells : meeting the needs for cell therapy[J].Adv Drug Deliv Rev, 2005, 57(13) : 1935-1943
  • 3程小星,蹇锐,邓少丽,蒋静.RNA干扰文库及其在功能基因组学研究中的应用[J].生物化学与生物物理进展,2005,32(3):195-198. 被引量：2
  • 4Jian R, Cheng X, Jiang J, et al. A cDNA-based random RNA interference library for functional genetic screens in embryonic stem cells[J]. Stem Cells, 2007, 25(8):1904-1912
  • 5Kittler R, Surendranath V, Heninger A K, et al. Genome-wide resunrces of endoribunuclease-preparedshort interfering RNAs for specific loss-of-function studies[J]. Nat Methods, 2007, 4(4):337- 344
  • 6Ovcharenko D, Kelnar K, Johnson C, et al. Genome-scale microRNA and small interfering RNA screens identify small RNA modulators of TRAIL-induced apoptosis pathway [ J ]. Cancer Res, 2007,67(22) : 10782-10788
  • 7Strat A, Gao L, Utsuki T, et al. Specific and nontoxic silencing in mammalian cells with expressed long dsRNAs[J]. Nucl Acids Res, 2006, 34(13) :3803-3810
  • 8Konstantinova P, de Vfies W, Haasnoot J, et al. Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA[J]. Gene Ther, 2006, 13(19):1403-1413
  • 9Yang S, Tutton S, Pierce E, et al. Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells[ J]. Mol Cell Biol, 2001, 21(22):7807-7816
  • 10Wianny F, Zemicka-Goetz M. Specific interference with gene function by double-stranded RNA in early mouse development [J]. Nat Cell Biol, 2000, 2(2) :70-75

二级参考文献22

  • 1蹇锐,程小星,彭涛,邓少丽,蒋静.U6和H1双启动子载体用于RNAi的实验研究[J].中国生物工程杂志,2004,24(11):26-29. 被引量：7
  • 2Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. 2004, Nature, 431 (7006): 343～349.
  • 3Hannon G J, Rossi J J. Unlocking the potential of the human genome with RNA interference. Nature, 2004, 431 (7006): 371～378.
  • 4Elbashir S M, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleofide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411 (6836): 494～498.
  • 5Brummelkemp T R, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science,2002, 296 (5567): 550～553.
  • 6Miyagishi M, Taira K. U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress targeted gene expression in mammalian cells. Nature Biotechnology, 2002, 20 (5): 497～500.
  • 7Xia H, Mao Q, Paulson H L, et al. siRNA-mediated gene silencing in vitro and in vivo. Nature Biotechnology, 2002, 20 (10): 1006～1010.
  • 8Kamath R S, Fraser A G, Dong Y, et al. Systematic functional analysis of the Caenorhadbitis elegans genome using RNAi. Nature,2003, 421 (6920): 231～237.
  • 9Boutros M, Kiger A A, Armknecht S, et al. Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science, 2004,303 (5659): 832～835.
  • 10Nollen E A A, Garcia S M, van Haaften G, et al. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation. Proc Natl Acad Sci USA, 2004, 101(17): 6403～6408.

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中国生物化学与分子生物学报
2008年 第10期

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