重编程路线图揭示了人类诱导的热囊细胞干细胞的途径
Xiaodong Liu1,2,3, John F Ouyang4, Fernando J Rossello1,2,3,5
1Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
Nature
|September 17, 2020
概括
研究人员绘制了人体细胞重编程的地图,揭示了多能性的不同途径,并使人体细胞直接产生诱导的热囊细胞干细胞.
科学领域:
- 细胞生物学
- 发育生物学
- 基因组学
背景情况:
- 人体体细胞重新编程到诱导多能干细胞 (iPSC) 模仿早期胚胎发育,但缺乏机理性理解.
- 这种知识差距阻碍了重新编程协议的优化和开发过程的理解.
研究的目的:
- 将人类体细胞重新编程成原始和天真的多能状态的分子机制阐明.
- 确定这些不同的重编程轨迹中涉及的关键监管元素和转录因素.
- 在重新编程过程中探索衍生新型干细胞的潜力.
主要方法:
- 单细胞转录组学用于重建分子重编程轨迹.
- 对可访问的染色体进行全基因组分析,以确定调控元素的变化.
- 转录基因和表观基因数据的综合分析.
主要成果:
- 通过不同的分子路径进行重新编程.
- 在多能性基因的调节元件中观察到显著的染色质可访问性变化.
- 鉴定并捕获了一种类似于多叶皮的细胞状态,从而产生诱导的多叶细胞干细胞 (iTSC).
- 衍生的iTSC与自然存在的热囊细胞具有分子和功能上的相似性.
结论:
- 建立了一个高分辨率的转录因子介导的人体细胞重编程路线图.
- trofhectoderm 血统调节程序在体细胞重编程中起作用.
- 将体细胞直接重新编程为iTSC是可行的,为干细胞研究和应用提供了新的途径.
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