表观遗传重编程使从原始生殖细胞转变为血细胞
Peter W S Hill1,2, Harry G Leitch1,2, Cristina E Requena1,2
1MRC London Institute of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK.
Nature
|March 8, 2018
概括
科学家发现了关键的表观遗传机制, 这项研究阐明了原始生殖细胞 (PGC) 如何转化为血球细胞,
科学领域:
- 发育生物学
- 表观遗传学
- 遗传学
背景情况:
- 在小鼠中,原始生殖细胞 (PGC) 在胚胎6.25日左右被指定,并迁移到正在发育的性腺.
- 在胚胎10.5-11.5日左右,PGC会经历显著的表观遗传重编,包括DNA脱甲基化.
- 这种生殖系重编程的分子基础在很大程度上是未知的,这阻碍了体外生殖的复制.
研究的目的:
- 在小鼠的PGC转基因细胞转换过程中阐明表观遗传重编程的分子机制.
- 确定涉及全基因组DNA脱甲基和生殖细胞中的基因激活的因素和过程.
- 在体外复制生殖线发展的洞察力.
主要方法:
- 使用综合方法,结合促进子序列,DNA甲基化和多 (PRC1) 复合物的分析.
- 研究了TET1的作用,包括其DNA脱甲基化依赖和独立的功能.
- 检查了生殖系重编程响应基因的基因激活模式.
主要成果:
- 在激活关键生殖基因时,证明了促进体特征,DNA (去甲基化),PRC1和TET1功能之间的协调相互作用.
- 发现TET1在维持DNA脱甲基化方面起作用,但并没有在淋巴细胞PGC中启动该过程.
- 在此过渡过程中确定了一组关键的基因,
结论:
- 这项研究揭示了淋巴细胞生殖系重编程的基本生物学作用.
- 确定了控制PGC转变为血球细胞的关键表观遗传原理.
- 这些发现为未来的试验提供了指导,以便在体外进行完整的游戏生成.
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