胚胎干细胞的强度随着内源性逆转录病毒活动的波动而波动
Todd S Macfarlan1, Wesley D Gifford, Shawn Driscoll
1Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, California 92037, USA.
Nature
|June 23, 2012
概括
研究人员在小鼠培养物中发现了罕见的双细胞 (2C) 类干细胞. 这些细胞与典型的多能干细胞不同,可以形成胚胎和胚胎外组织,为早期发育和细胞命运调节提供新的见解.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 基因组学就是基因组学.
背景情况:
- 胚胎干细胞 (ES) 来自胚芽细胞,类似于内部细胞质,但不能形成所有的胚胎外组织.
- 在ES细胞中的多能性通常与特定的蛋白质标记物如Oct4,Sox2和Nanog.有关.
研究的目的:
- 在小鼠ES和诱导多能干细胞 (iPS) 细胞培养物中识别和表征一种罕见的细胞群.
- 为了研究分子机制和细胞法特调节,控制这种短暂的全能类状态.
主要方法:
- 在ES和iPS培养物中对罕见细胞进行遗传标记.
- 对多能蛋白表达的分析 (Oct4, Sox2, Nanog).
- 对胚胎和胚胎外组织的贡献的评估.
- 转录组测序和2C类细胞的生物信息分析.
- 研究基因素修饰酶的作用.
主要成果:
- 在小鼠ES和iPS细胞中发现了一种罕见的,短暂的细胞群体表达双细胞 (2C) 胚胎转录.
- 这些类似2C的细胞缺乏关键的多能性标记物 (Oct4,Sox2,Nanog) 并且表现出全能性,有助于胚胎和胚胎外血统.
- 几乎所有ES细胞都被观察到通过这种全能类状态循环,受到基因素修饰酶的影响.
- 生物信息分析显示,许多2C转录源于内源性逆转录病毒长端重复,这表明它们在细胞命运调节中的作用.
结论:
- 在标准小鼠ES和iPS细胞培养物中存在一种短暂的全能类状态,与典型的多能状态不同.
- 这种由表观遗传因素和潜在的内源性逆转录病毒元素调节的2C类状态,扩大了干细胞的发育潜力.
- 了解这种状态为早期哺乳动物发育和细胞命运可塑性提供了新的见解,用于再生医学应用.
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