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人类多能干细胞中的获得性遗传和表观遗传变异

Acquired Genetic and Epigenetic Variation in Human Pluripotent Stem Cells.

作者信息

Kyriakides O, Halliwell J A, Andrews P W

机构信息

Centre for Stem Cell Biology, Department Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.

出版信息

Adv Biochem Eng Biotechnol. 2018;163:187-206. doi: 10.1007/10_2017_22.

DOI:10.1007/10_2017_22
PMID:29071402
Abstract

Human pluripotent stem cells (hPSCs) can acquire non-random genomic variation during culture. Some of these changes are common in tumours and confer a selective growth advantage in culture. Additionally, there is evidence that reprogramming of human induced pluripotent stem cells (hiPSCs) introduces mutations. This poses a challenge to both the safety of clinical applications and the reliability of basic research using hPSCs carrying genomic variation. A number of methods are available for monitoring the genomic integrity of hPSCs, and a balance between practicality and sensitivity must be considered in choosing the appropriate methods for each use of hPSCs. Adjusting protocols by which hPSCs are derived and cultured is an evolving process that is important in minimising acquired genomic variation. Assessing genetic variation for its potential impact is becoming increasingly important as techniques to detect genome-wide variation improve.

摘要

人类多能干细胞(hPSC)在培养过程中会获得非随机的基因组变异。其中一些变化在肿瘤中很常见,并在培养中赋予选择性生长优势。此外,有证据表明人类诱导多能干细胞(hiPSC)的重编程会引入突变。这对临床应用的安全性以及使用携带基因组变异的hPSC进行基础研究的可靠性都构成了挑战。有多种方法可用于监测hPSC的基因组完整性,在为hPSC的每次使用选择合适方法时,必须考虑实用性和敏感性之间的平衡。调整hPSC的来源和培养方案是一个不断发展的过程,这对于最小化获得性基因组变异很重要。随着检测全基因组变异的技术不断改进,评估遗传变异的潜在影响变得越来越重要。

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