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复制数的变化和选择在重编程到多能性的过程中.

Samer M Hussein1, Nizar N Batada, Sanna Vuoristo

  • 1Samuel Lunenfeld Research Institute, Toronto, Ontario M5T 3H7, Canada.

Nature
|March 4, 2011
PubMed
概括

诱导的多能干细胞 (iPS) 重编程在早期通道中产生拷贝数变异 (CNV),损害了基因组完整性. 然而,细胞培养迅速选择这些遗传变化,随着时间的推移改善iPS细胞质量.

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科学领域:

  • 干细胞生物学 干细胞生物学
  • 基因组学就是基因组学.
  • 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

  • 将体细胞重新编程成诱导多能干细胞 (iPS) 的低效率仍然是一个重大挑战.
  • 了解影响重编程效率的因素,特别是基因组完整性,对于推进再生医学至关重要.

研究的目的:

  • 调查重新编程过程本身是否导致基因组不稳定.
  • 描述iPS细胞生成和培养过程中遗传变化的性质和影响.

主要方法:

  • 利用高分辨率单核酸多态 (SNP) 阵列来分析副本数变异 (CNV).
  • 在人类iPS细胞的不同通道中的CNV与其原始纤维细胞和人类胚胎干细胞 (ES) 进行了比较.

主要成果:

  • 早期通过的人类iPS细胞与中间通过iPS细胞,纤维细胞和人体ES细胞相比,表现出显著更多的CNV.
  • 大多数NVs de novo出现,在早期通道iPS细胞中产生遗传马赛克,许多细胞具有选择性劣势.
  • 在体外扩张人类iPS细胞快速选择与具有CNVs的细胞.

结论:

  • 重编程过程可以诱导基因组的不稳定性,由早期通道iPS细胞中的新型CNVs证明.
  • 细胞培养和扩张施加选择性压力,有利于基因稳定的细胞,并随着时间的推移提高iPS细胞系的质量.
  • 这些发现为影响iPS细胞效率和基因组完整性的机制提供了关键的见解.