Stem Cell Epigenetics: Insights from Studies on Embryonic, Induced Pluripotent, and Germline Stem Cells

Stem Cell Epigenetics: Insights from Studies on Embryonic, Induced Pluripotent, and Germline Stem Cells
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DOI:
10.1007/s40139-013-0038-3
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发表时间:
2014-01
影响因子:
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通讯作者:
Shin-ichi Tomizawa;Takayuki Shirakawa;K. Ohbo
Shin-ichi Tomizawa;Takayuki Shirakawa;K. Ohbo
中科院分区:
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文献类型:
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作者:
Shin-ichi Tomizawa;Takayuki Shirakawa;K. Ohbo

文献摘要

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胚胎干细胞和诱导多能干细胞(iPSCs)表现出相似和独特的表观遗传特征,赋予它们多能性。多能细胞具有高度可塑性的基因组,其显示的开放染色质大量被活性组蛋白修饰标记,使其为分化线索做好准备。这与谱系细胞相反,谱系细胞具有凝聚的异染色质和大块的抑制染色质结构域。最近对精原干细胞的一项研究表明,在分化过程中会发生动态的表观遗传变化,这表明在胚胎型和成体型干细胞中,全局表观遗传调控在干细胞和分化细胞之间起着屏障作用。重编程需要克服这种表观遗传障碍,以建立忠实的基因表达模式。有证据表明,不完全表观遗传重编程在ipsc中很常见,这突出了临床应用中潜在的严重问题。在这里,我们回顾了体外干细胞研究的见解和主要进展,以及生殖系干细胞的体内表征。
Embryonic stem cells and induced pluripotent stem cells (iPSCs) exhibit similar and unique epigenetic features that endow them with pluripotency. Pluripotent cells have highly plastic genomes that display open chromatin that is abundantly marked by active histone modifications, making it poised for differentiation cues. This is in contrast to lineage-committed cells, which have condensed heterochromatin and large blocks of repressive chromatin domains. A recent study of spermatogonial stem cells showed dynamic epigenetic changes occur during differentiation, suggesting that, in both embryonic- and adult-type stem cells, global epigenetic regulation serves as a barrier between stem and differentiated cells. Reprogramming requires that this epigenetic barrier be overcome for faithful gene expression patterns to be established. Evidence suggests that incomplete epigenetic reprogramming is common in iPSCs, highlighting potentially serious problems for clinical applications. Here, we review insights and major progress obtained from in vitro stem cell studies, as well as in vivo characterization of stem cells in the germline.