决定性直接重编程体细胞到多能性
Yoach Rais1, Asaf Zviran, Shay Geula
1The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Nature
|September 20, 2013
概括
将体细胞重新编程成诱导多能干细胞 (iPS) 通常是低效的. 耗尽Mbd3可以提高Oct4,Sox2,Klf4和Myc (OSKM) 的重编程效率接近100%,从而创建一个决定性和同步的过程.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子重编程是一种分子重编程.
背景情况:
- 使用Oct4,Sox2,Klf4和Myc (OSKM) 将体细胞重新编程成诱导多能干细胞 (iPS) 细胞通常是低效和随机的.
- 对高效和同步重编程的主要障碍在很大程度上仍未确定.
研究的目的:
- 为了研究体细胞重编程的速度限制因素.
- 开发一种确定性和同步iPS细胞生成的方法.
主要方法:
- 在体细胞中OSKM因子的外源表达.
- 耗尽Mbd3,这是Mbd3/NuRD抑制器综合体的一个组成部分.
- 在幼稚的多能性促进条件下进行重编程.
主要成果:
- 随着OSKM转导而耗尽Mbd3,在7天内实现了确定性和同步的iPS细胞重编程,效率接近100%.
- 确定了重编程因子的二分功能:重新激活多能网络和招募Mbd3/NuRD复合体来抑制目标基因的重新激活.
- 证明了在早期发育过程中减少的Mbd3/NuRD复杂相互作用,有助于体外重编程的随机性.
结论:
- Mbd3作为一个关键抑制器,限制了OSKM调度重编程的效率和同步性.
- 开发的确定性重编程方法为研究多能建立提供了一个强大的平台.
- 了解Mbd3/NuRD的作用为控制细胞重编程动态提供了新的见解.
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