Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and Their Differentiated Derivatives

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• 作者：Kristopher  ; L. Nazor¹ ; Gulsah Altun¹ ; ¹⁵ ; Candace Lynch¹ ; ¹⁴ ; Ha Tran¹ ; ¹⁴ ; Julie  ; V. Harness² ; ¹⁴ ; Ileana Slavin¹ ; Ibon Garitaonandia¹ ; ¹⁶ ; Franz-Josef Mü ; ller¹ ; ³ ; Yu-Chieh Wang¹ ; Francesca  ; S. Boscolo¹ ; Eyitayo Fakunle¹ ; ¹⁷ ; Biljana Dumevska⁴ ; Sunray Lee⁵ ; Hyun  ; Sook Park⁶ ; ¹⁸ ; Tsaiwei Olee⁷ ; Darryl  ; D. D'Lima⁷ ; Ruslan Semechkin⁸ ; Mana  ; M. Parast⁹ ; Vasiliy Galat¹¹ ; Andrew  ; L. Laslett¹² ; ¹³ ; Uli Schmidt⁴ ; Hans  ; S. Keirstead² ; Jeanne  ; F. Loring¹ ; ¹⁰ ; Louise  ; C. Laurent¹ ; ¹⁰ ; ^{llaurent@ucsd.edu}
• 刊名：Cell Stem Cell
• 出版年：2012
• 期刊代码：P15_19345909
• 类别：bio
• 出版时间：4 May, 2012
• 卷：10
• 期：5
• 页码：620-634
• 文件大小：3187 K

摘要

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lass="h3">Summary

Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to聽X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by聽DNA demethylation during in聽vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based聽disease models in which the observed phenotype depends on proper XCI or imprinting and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.