染色体修饰酶作为重编程调节器
Tamer T Onder1, Nergis Kara, Anne Cherry
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|March 6, 2012
概括
研究人员确定了影响诱导多能干细胞 (iPSC) 生成的特定染色质修饰酶. 抑制DOT1L,一种组胺甲基转移酶,加速了重新编程和增加了iPSC产量,为高效的iPSC生产提供了一个新的策略.
科学领域:
- 表观遗传学和干细胞生物学
- 染色体修饰和基因调控
- 细胞重编程机制 细胞重编程机制
背景情况:
- 将体细胞重编程为诱导的多能干细胞 (iPSCs) 涉及到广泛的表观遗传重塑.
- 在这个过程中,特定的染色质修饰酶的作用尚未完全理解.
- 识别关键监管者可以优化iPSC发电效率.
研究的目的:
- 研究染色质修饰酶如何影响诱导多能干细胞 (iPSC) 生成的效率.
- 识别在重编程过程中作为障碍物或促进者的特定酶.
- 通过针对性的表观遗传调制,探索增强iPSC生产的策略.
主要方法:
- 利用短发针RNAs (shRNAs) 来准DNA和基因组甲基化途径中的基因.
- 评估了抑制各种染色质修饰酶对iPSC生成效率的影响.
- 在重编程过程中对H3K79二甲基化 (H3K79me2) 分布进行了全基因组分析.
主要成果:
- 包括EZH2在内的Polycomb Repressive Complex 1和2组件的抑制降低了重新编程的效率.
- 抑制SUV39H1,YY1和DOT1L的增强重编程.
- DOT1L抑制加速了重新编程,增加了iPSC产量,并替代了KLF4和c-Myc,与增加的NANOG和LIN28水平相关.
结论:
- 特定的染色质修饰酶在体细胞重编程中扮演关键角色,作为障碍物或促进者.
- DOT1L抑制成为提高iPSC发电效率和产量的有效策略.
- 准染色体修饰通路提供了一种有前途的方法,可以通过更少的重编程因子来改善iPSC的生产.
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