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Cell Stem Cell：科学家找到维持皮肤干细胞功能的两个蛋白“守卫”

2016-07-30 佚名 生物谷

皮肤干细胞
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我们的皮肤可以自我更新，治愈伤口还可以再生毛发，这都得益于一小群皮肤干细胞的存在。这些干细胞会持续产生新细胞，在随后几天它们会出现在皮肤表面。一项发表在国际学术期刊Cell Stem Cell上的最新研究发现两个同家族蛋白构成了皮肤干细胞存在的重要基础，如果没有这两种蛋白皮肤干细胞也将不会存在。 研究人员发现的这两个蛋白就是DNA甲基化酶Dnmt3a和Dnmt3b，它们对于皮肤干细胞的自

我们的皮肤可以自我更新，治愈伤口还可以再生毛发，这都得益于一小群皮肤干细胞的存在。这些干细胞会持续产生新细胞，在随后几天它们会出现在皮肤表面。一项发表在国际学术期刊Cell Stem Cell上的最新研究发现两个同家族蛋白构成了皮肤干细胞存在的重要基础，如果没有这两种蛋白皮肤干细胞也将不会存在。

 研究人员发现的这两个蛋白就是DNA甲基化酶Dnmt3a和Dnmt3b，它们对于皮肤干细胞的自我更新有至关重要的作用，它们能够启动干细胞基因编程的第一步。研究人员表示：“如果没有它们，干细胞的编程就不会激活，干细胞就会从组织中消失。”

在该研究中研究人员找遍了基因组中结合了这两种蛋白的各个区域。他们观察到这两个蛋白在基因的增强子和超级增强子上发挥它们的活性，虽然增强子和超级增强子都距离它们调控的基因很远，但能够起到非常强的增强转录作用。

“这两个蛋白经常通过DNA甲基化实现对基因的抑制，因此我们非常惊讶地看到这两个蛋白会在干细胞转录最活跃的区域发生激活。由于之前无法研究Dnmt3a和Dnmt3b在整个基因组中的分布，因此我们也从未观察到上述现象。因为测序技术的进步，会有越来越多的科研工作者看到我们描述的这种机制。”

基因组的12000多个增强子中有大约300个是与干细胞相关的超级增强子。这两种蛋白通过DNA甲基化修饰在这些区域发挥它们的功能，从而增强了大约1000个干细胞自我更新所需要的基因表达。

与癌症相关

癌细胞有许多不同特征。首先癌细胞存在DNA甲基化的改变，其次不仅基因本身发生突变基因增强子也存在高度突变。这些发现都得益于对肿瘤细胞基因组的大规模测序才成为可能。第三，Dnmt3a和Dnmt3b这两种蛋白的表达在许多类型的肿瘤中都存在改变。

作者最后总结道：“上述三点都与多种类型癌症的发生有关，考虑到这些蛋白通过DNA甲基化调节增强子增强基因表达，我们相信研究这两个蛋白在癌细胞中的作用进一步确定它们是否参与肿瘤发生将会非常有趣。”

原始出处

Lorenzo Rinaldi, Debayan Datta, Judit Serrat, Lluis Morey, Guiomar Solanas, Alexandra Avgustinova, Enrique Blanco, José Ignacio Pons, David Matallanas, Alex Von Kriegsheim, Luciano Di Croce.Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis.Cell Stem Cell.2016

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    2016-12-30 zhaozhouchifen

    #Cell#

    0

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    2016-10-04 hb2008ye

    #stem cell#

    0

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    2017-05-19 维他命

    #CEL#

    0

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    2016-08-01 12498bb3m92(暂无昵称)

    #STEM#

    0

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    2016-08-01 般若傻瓜

    #细胞功能#

    0