科学家揭示对胚胎干细胞分化至关重要的特殊基因

  近日，来自新加坡A*STAR研究所的研究人员通过研究发现，染色质重塑基因Chd1可以调节胚胎干细胞发育成为其它类型细胞的能力。研究者表示，名为磷酸化作用的常见翻译后修饰机制与细胞内蛋白质功能的调节及信号传输存在一定的关联，这或许会影响依赖Chd1的细胞命运的改变，相关研究成果刊登在国际杂志Scientific Reports上。
  真核细胞细胞核中染色质的重塑对于胚胎干细胞分化成为多种类型的细胞至关重要，而Chd1的活性可以通过对蛋白质N端区域的磷酸化作用来特异性调节，本文研究就发现当这一区域被剔除后，细胞就会出现异常的分化表型。
  文章中，研究者Lim及其同事利用小鼠胚胎干细胞进行了一项深度研究，研究者剔除了Chd1基因负责编码Chd1蛋白的片段，该区域的剔除会导致缺失N末端区域的Chd1蛋白变短；而当这种被截短的蛋白在小鼠胚胎干细胞中进行表达时研究者就能够在体外的模型中观察到异常的分化表型。
  进行体内试验研究者发现，携带移除Chd1 N末端突变的小鼠会正常发育，而且是可育的；然而Chd1突变小鼠产生的胚胎干细胞却和体外产生的胚胎干细胞一样能够表现出相同的倾向，分化成为神经元样的细胞，这就表明多种因子参与了体内的实验环境，比如不同的生长信号，其往往会隐藏Chd1突变引发的缺失现象。
  研究者Lim说道，我们的研究结果表明，当细胞进行分化时，磷酸化作用或许对于Chd1进行胚胎干细胞的自我更新、改变Chd1的活性并不是很必要；本文研究阐明了控制胚胎干细胞的新途径，胚胎干细胞向临床相关的细胞类型的直接分化或许可以通过改变染色质重塑因子（比如Chd1）来进行细微地调整。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Embryonic stem cell differentiation requires full length Chd1
Scientific Reports             doi:10.1038/srep08007
Paolo Piatti, Chin Yan Lim, Roxana Nat, Andreas Villunger, Stephan Geley, Yan Ting Shue, Claudia Soratroi, Markus Moser & Alexandra Lusser
The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1Δ2/Δ2 mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.