Genetic and epigenetic instability in human pluripotent stem cells

被引：64
作者：
Nguyen, H. T. [1 ]
Geens, M. [1 ]
Spits, C. [1 ]
机构：
[1] Vrije Univ Brussel, Res Grp Reprod & Genet, B-1090 Brussels, Belgium
来源：
HUMAN REPRODUCTION UPDATE | 2013年 / 19卷 / 02期
关键词：
genome integrity; human pluripotent stem cells; epigenetics; malignancy; differentiation capacity; X-CHROMOSOME INACTIVATION; IN-VITRO; ES CELLS; CULTURE ADAPTATION; DNA METHYLATION; CD30; EXPRESSION; CANCER-CELLS; LINES; REVEALS; MOUSE;
D O I：
10.1093/humupd/dms048
中图分类号：
R71 [妇产科学];
学科分类号：
100211 ;
摘要：
BACKGROUND: There is an increasing body of evidence that human pluripotent stem cells (hPSCs) are prone to (epi)genetic instability during in vitro culture. This review aims at giving a comprehensive overview of the current knowledge on culture-induced (epi)genetic alterations in hPSCs and their phenotypic consequences. METHODS: Combinations of the following key words were applied as search criteria: human induced pluripotent stem cells and human embryonic stem cells in combination with malignancy, tumorigenicity, X inactivation, mitochondrial mutations, genomic integrity, chromosomal abnormalities, culture adaptation, aneuploidy and CD30. Only studies in English, on hPSCs and focused on (epi)genomic integrity were included. Further manuscripts were added from cross-references. RESULTS: Numerous (epi)genetic aberrations have been detected in hPSCs. Recurrent genetic alterations give a selective advantage in culture to the altered cells leading to overgrowth of abnormal, culture-adapted cells. The functional effects of these alterations are not yet fully understood, but suggest a (pre)malignant transformation of abnormal cells with decreased differentiation and increased proliferative capacity. CONCLUSIONS: Given the high degree of (epi)genetic alterations reported in the literature and altered phenotypic characteristics of the abnormal cells, controlling for the (epi)genetic integrity of hPSCs before any clinical application is an absolute necessity.
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收藏
页码：187 / 205
页数：19
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