Stem Cell Rep：抑制DNA甲基化调控因子让iPSC更像ESC

2016-07-07 佚名生物谷

本文亮点：抑制miR-29a家族表达能够提高体细胞重编程效率 DNA去甲基化是抑制miR-29a表达之后诱导产生的主要变化 CpG岛周围的甲基化受到miR-29a家族的高度调控抑制miR-29a家族表达后获得的诱导多能干细胞在表观遗传水平上与胚胎干细胞非常接近近日，来自美国耶鲁干细胞中心的研究人员在国际学术期刊Stem Cell

本文亮点：

抑制miR-29a家族表达能够提高体细胞重编程效率
DNA去甲基化是抑制miR-29a表达之后诱导产生的主要变化
CpG岛周围的甲基化受到miR-29a家族的高度调控
抑制miR-29a家族表达后获得的诱导多能干细胞在表观遗传水平上与胚胎干细胞非常接近

近日，来自美国耶鲁干细胞中心的研究人员在国际学术期刊Stem Cell Reports上发表了一项最新研究进展，他们发现一个microRNA家族在体细胞重编程过程中对DNA甲基化水平起到了重要调节作用，抑制该microRNA能够使诱导多能干细胞的DNA甲基化水平更加接近胚胎干细胞。该研究对优化诱导多能干细胞的重编程条件，获得更适于临床应用的iPSC具有重要意义。

过表达Yamanaka四因子（OCT4,SOX2,KLF4以及MYC）诱导体细胞重编程获得多能干细胞的过程还会伴随着整个基因组和表观遗传组学的变化。之前研究已经表明诱导多能干细胞的组蛋白修饰和DNA甲基化水平与胚胎干细胞高度相似，但是这两种干细胞仍然存在表观遗传学的差异。特别是诱导多能干细胞的DNA甲基化水平存在异常，这也是诱导多能干细胞在临床应用方面的一个主要顾虑。因此找出重编程过程中调节DNA甲基化水平的因子具有重要意义。

在这项研究中研究人员发现miR-29家族是人类体细胞重编程过程中一个重要的表观遗传调控因子，他们通过global DNA甲基化和羟甲基化分析发现DNA去甲基化是重编程早期抑制miR-29a表达介导的一个主要事件，抑制miR-29a之后获得的诱导多能干细胞在表观遗传水平更加接近胚胎干细胞。

总的来说，该研究揭示了miRNA在体细胞重编程获得多能干细胞过程中对表观遗传修饰的重要调控作用，为获得更适于临床应用的诱导多能干细胞提供了潜在方法。

原始出处：

Hysolli E, Tanaka Y, Su J, Kim KY, Zhong T, Janknecht R, Zhou XL, Geng L, Qiu C, Pan X, Jung YW, Cheng J, Lu J, Zhong M, Weissman SM, Park IH.Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by themiR-29 Family.Stem Cell Reports. 2016 Jun 30. pii: S2213-6711(16)30069-8. doi: 10.1016/j.stemcr.2016.05.014. [Epub ahead of print]

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2017-02-15 维他命

#CEL#

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2017-01-05 医者仁心

#Cell#

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2017-02-14 hb2008ye

#stem cell#

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2016-07-09 chengjn

#iPS#

48 0
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2016-07-09 gjsgj

#PSC#

57 0
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2016-07-09 12498bb3m92(暂无昵称)

#STEM#

41 0
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2016-07-09 neurosurgeon

#iPSC#

61 0

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