在诱导多能干细胞干细胞中的表观遗传记忆
1Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Nature
|July 21, 2010
概括
体细胞核转移 (SCNT) 在实现多能性方面比基于转录因子的重编程更有效. 从SCNT衍生的细胞表现出较少的表观遗传记忆,与诱导多能干细胞 (iPSCs) 相比,使得更广泛的分化潜力.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
- 发展生物学 发展生物学
背景情况:
- 体细胞核转移 (SCNT) 和基于转录因子的重编程是从成体细胞生成多能干细胞的方法.
- 这两种方法都重置了基因组甲基化,一种影响基因表达的表观遗传修饰.
- 重编程机制的差异表明,由此产生的多能干细胞的特性可能有所变化.
研究的目的:
- 研究SCNT衍生和诱导多能干细胞 (iPSCs) 之间的表观遗传状态和差异化潜力的差异.
- 确定源代体组织的表观遗传记忆是否影响iPSCs的特性.
- 为了比较SCNT和基于因素的重编程在确定多能性的基本状态方面的有效性.
主要方法:
- 在低通道iPSC和SCNT衍生的多能干细胞中比较DNA甲基化模式.
- 评估不同细胞系的分化潜力.
- 用染色体修饰药物治疗iPSC,以调查表观遗传记忆重置.
主要成果:
- iPSCs保留其源体组织的残留DNA甲基化特征,有利于供体特异化.
- 这种iPSC中的"表观遗传记忆"限制了替代细胞命运,但可以重置.
- 由SCNT衍生的多能干细胞表现出与胚胎干细胞相比更类似的分化和甲基化模式.
结论:
- 在建立多能性的基本状态方面,SCNT比基于因素的重编程更有效.
- 基于因素的重编程可以留下影响定向差异化的表观遗传记忆.
- 了解这些表观遗传差异对于疾病建模和再生医学的应用至关重要.
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