在体内重新编程的过早终止会通过改变表观遗传调节导致癌症的发展
Kotaro Ohnishi1, Katsunori Semi2, Takuya Yamamoto2
1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Cell
|February 18, 2014
概括
在体内,重编程因子的短暂表达可以诱导瘤. 这些由表观遗传变化驱动的瘤类似于某些癌症,但在遗传上并非不可逆转,这表明干细胞重编程和癌症发展之间存在联系.
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
- 癌症生物学 癌症生物学
背景情况:
- 癌症传统上与遗传突变有关.
- 诱导多能干细胞 (iPSC) 与癌细胞具有无限的生长潜力,尽管缺乏遗传突变.
- 重编程因素可以诱导多能性和无限增长.
研究的目的:
- 为了研究短暂表达的重编程因子的体内影响.
- 为了确定在iPSC生成过程中的表观遗传变化是否会导致癌症.
- 探索表观遗传调节与癌症发展之间的关系.
主要方法:
- 开发了一种可诱导多西环素的小鼠系统,用于实体内对重编程因子表达的时间控制.
- 给出了多西环林来诱导重编程因子的表达,随后取消了它来观察瘤的发展.
- 分析瘤细胞特征,包括DNA甲基化模式和分化潜力.
- 从瘤细胞中获得iPSC,并评估它们在体内形成非新生组织的能力.
主要成果:
- 重编程因子在体内短暂的表达导致了各种组织中的瘤形成.
- 瘤包括无差异的,具有全球DNA甲基化变化的失生细胞.
- 脱离多西环林的小鼠的脏瘤与威尔姆斯瘤相似,这是儿童脏癌症.
- 来自这些瘤细胞的iPSCs可以分化为非新生细胞,表明缺乏不可逆转的遗传转变.
结论:
- 在iPSC生成期间表观遗传失调可以驱动特定癌症类型的发展.
- 由重编程因素诱导的瘤发生可能是可逆的,这表明表观遗传学而不是仅仅遗传突变的作用.
- 这些发现突出了干细胞可塑性和癌症发作之间的潜在联系,特别是在表观遗传驱动的癌症中.
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