人类和猿类多能干细胞中的差异L1调节
Maria C N Marchetto1, Iñigo Narvaiza1, Ahmet M Denli1
1Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nature
|October 25, 2013
概括
诱导多能干细胞 (iPS) 揭示了人类和非人类灵长类动物 (NHPs) 之间长间隔的元素-1 (L1) 转位子活性的差异. 这些发现表明,L1移动性变异可能会推动大猿的进化适应和物种化.
科学领域:
- 进化生物学是进化的生物学.
- 基因组学就是基因组学.
- 干细胞研究的研究.
背景情况:
- 人类和非人类灵长类动物 (NHP) 进化的比较研究传统上依赖于保存的组织,限制了对活细胞行为和遗传操纵的洞察力.
- 诱导多能干细胞 (iPS) 为研究表型差异及其在适应和物种化中的潜在作用提供了一个新的生物资源.
研究的目的:
- 来自黑猩猩和黑猩猩的iPS细胞作为探索大猿进化的工具来生成和表征.
- 研究人类和NHP iPS细胞之间的细胞和分子差异,特别是长间隔的元素-1 (L1) 转位子的调节.
主要方法:
- 黑猩猩和黑猩猩 iPS 细胞的生成和表征.
- 对人类和NHP iPS细胞进行基因表达的比较分析.
- 研究L1逆转移素活性和L1限制因子 (APOBEC3B/A3B和PIWIL2) 的作用.
主要成果:
- 与人类iPS细胞相比,NHP iPS细胞表现出L1限制因子 (A3B和PIWIL2) 的水平降低.
- 这些因素的较低水平与NHP iPS细胞中L1流动性增加和内源L1信使RNA水平相关.
- 在黑猩猩基因组中发现了特定物种L1元素的复制量增加,这表明L1流动性发生在细胞培养之外.
结论:
- 人类和NHP之间的L1转子子调节和移动性的差异可能已经显著塑造了灵长类动物基因组的进化.
- L1活动的变化可能是适应和物种化的关键因素,具有持续的适应意义.
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