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本帖最后由 f5_105 于 2013-3-9 18:52 编辑
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Hum Reprod Update. 2013 Mar;19(2):187-205. doi: 10.1093/humupd/dms048. Epub 2012 Dec 7.7 w5 G7 X) X9 y* y
Genetic and epigenetic instability in human pluripotent stem cells.
1 R1 R9 m% N% C& e, n( Z0 q4 g& e# fNguyen HT, Geens M, Spits C.4 b4 M; B( |, [- i; C0 f
Source
. ^' w% k1 Z& e: hResearch Group Reproduction and Genetics, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Jette, Brussels, Belgium.
6 f5 _5 N. v6 g6 h( g$ Z, T1 sAbstract
# m5 V. a& t0 o$ k8 u# TBACKGROUND 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./ L3 J$ ?' ~- Y# @
PMID: 23223511 [PubMed - in process]
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/ s. R' Y# G I, k3 k: V+ U L8 Ahttp://humupd.oxfordjournals.org/content/19/2/187.long
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