核化定义了诱导多能性的最佳区域
Palas K Chanda1, Shu Meng1, Jieun Lee2
1Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, TX (P.K.C., S.M., K.C., J.P.C.).
Circulation
|August 16, 2019
概括
天生的免疫激活和氧化物 (NO) 产生为表观遗传可塑性创造最佳的"金发区",增强诱导的多能干细胞生成. 这种平衡对于核重编程和细胞命运至关重要.
科学领域:
- 表观遗传学和细胞生物学
- 遗传免疫和干细胞重编程
背景情况:
- 细胞自主天生的免疫信号影响核重编程到多能性的表观遗传修饰剂.
- 之前的研究表明,诱导性氧化 (NO) 合成酶对S- 化有作用.
研究的目的:
- 调查S-化在核重编程中的作用.
- 确定先天免疫激活,NO生成和诱导多能干细胞 (iPSC) 产量之间的关系.
主要方法:
- 在小鼠胚胎纤维细胞中利用多西环素诱导的Yamanaka因子表达.
- 使用可诱导的NO合成酶的基因/药理抑制,Tandem质量标记,ChIP-qPCR,位点定向突变和微球菌核酶测定.
主要成果:
- 由NF-κB激活,NO生成和S-化定义的先天免疫激活的最佳区域最大化了iPSC产量.
- 抑制可诱导的NO合成酶降低了DNA的可访问性和iPSC的产生.
- 包括MTA3在内的核蛋白的S- 化降低了NuRD复合物的活性,影响了DNA的可访问性和重编程.
结论:
- DNA可访问性和iPSC产量取决于先天免疫激活程度和NO生成.
- 炎症信号和表观遗传可塑性的"金发区"影响细胞命运和表型流动性.
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