Cell Stem Cell特刊：干细胞表观遗传学说

　　

生物通报道，英国剑桥大学，Wellcome Trust 癌症研究所Henry Wellcome 癌症与发育生物学研究中心的科学家发现小鼠多能干细胞具有不均一的分化潜能，这一机制受表观遗传学机理控制，相关文章发表在10月9日的Cell Stem Cell上。并被列为特刊文章（Featured Article）。

 

胚胎干细胞是一种具有自我更新能力的均一细胞系，但是科学家们观察到，胚胎干细胞中的stella表达却各不相同，stella是多能细胞和生殖细胞的生物学标记。研究者对stella表达的研究发现，stella阳性的胚胎干细胞发育成内胚层的细胞团，stella阴性的胚胎干细胞发育成外胚层细胞团。而这一情形情况（stella阳性或阴性）可以互换的，这也证实了胚胎干细胞的可塑性的确很强，这些胚胎干细胞都处于一个亚稳定状态，因此具有强可塑性。当饲养细胞释放出的信号发生改变的时候，已经建立稳定状态的干细胞也可发生改变，将导致外胚层细胞的生物标记发生改变。这一饲养细胞的改变来自古曲抑菌素A，它是一种histone deacetylase的抑制剂，可改变修复stella标记。

 

研究者发现，外胚层和内胚层的干细胞在组蛋白的修饰作用上有很大的差别，同时这些差别影响它们的功能，影响它们分化的趋势。Stella阴性的胚胎干细胞由EpiSCs（epiblast-derived stem cell）细胞系分化形成，这一细胞系的stella基因座被DNA甲基化机制所抑制，因此不表达stella，称为stella阴性。

 

这些结果表明，干细胞受多种表观遗传学机制影响，后生的调控，比如DNA甲基化，组蛋白修饰作用，对干细胞的功能具有深刻的影响，也许也是关键的影响。

 

原文摘要：Dynamic Equilibrium and Heterogeneity of Mouse Pluripotent Stem Cells with Distinct Functional and Epigenetic States

 

【Summary】

Embryonic stem cells (ESCs) are apparently homogeneous self-renewing cells, but we observed heterogeneous expression of Stella in ESCs, which is a marker of pluripotency and germ cells. Here we show that, whereas Stella-positive ESCs were like the inner cell mass (ICM), Stella-negative cells were like the epiblast cells. These states were interchangeable, which reflects the metastability and plasticity of ESCs. The established equilibrium was skewed reversibly in the absence of signals from feeder cells, which caused a marked shift toward an epiblast-like state, while trichostatin A, an inhibitor of histone deactelylase, restored Stella-positive population. The two populations also showed different histone modifications and striking functional differences, as judged by their potential for differentiation. The Stella-negative ESCs were more like the postimplantation epiblast-derived stem cells (EpiSCs), albeit the stella locus was repressed by DNA methylation in the latter, which signifies a robust epigenetic boundary between ESCs and EpiSCs.

生物通 张欢