@article{3c7d77c56b3a44d79571855fcd44a68a,
title = "Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives",
abstract = "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 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 DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based 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.",
author = "Nazor, {Kristopher L.} and Gulsah Altun and Candace Lynch and Ha Tran and Harness, {Julie V.} and Ileana Slavin and Ibon Garitaonandia and M{\"u}ller, {Franz Josef} and Wang, {Yu Chieh} and Boscolo, {Francesca S.} and Eyitayo Fakunle and Biljana Dumevska and Sunray Lee and Park, {Hyun Sook} and Tsaiwei Olee and D'Lima, {Darryl D.} and Ruslan Semechkin and Parast, {Mana M.} and Vasiliy Galat and Laslett, {Andrew L.} and Uli Schmidt and Keirstead, {Hans S.} and Loring, {Jeanne F.} and Laurent, {Louise C.}",
note = "Funding Information: We would like to gratefully acknowledge the following for contributing samples for this study: Juan-Carlos Belmonte, Eirini Papapetrou (Sadelain lab), Dongbao Chen, Jerold Chun, Martin Pera, James Shen, Scott McKercher, Timo Otonkoski, Allan Robins, Thomas Schulz, Philip Schwartz, Scott McKercher, Ralph Graichen, Jeong Beom Kim, Nils O. Schmidt, Christopher Barry, Robin Wesselschmidt, James Shen, Joel Gottesfeld, Christina Lu, the NICHD Brain and Tissue Bank for Developmental Disorders, and Planned Parenthood of the Pacific Southwest. We would also like to acknowledge Yinchun Li for generously contributing his expertise in histological evaluation of iPSC-derived teratomas. We would like to thank Trevor Leonardo, Robert Morey, Sara Abdelrahman, Inbar Friedrich Ben-Nun, Victoria Glenn, Dumitru Brinza, Dmitry Pushkarev, Tenneille Ludwig, and Kristen Brennand for their valuable help in the laboratory and for useful discussions. Many thanks to Marina Bibikova and Jian-Bing Fan at Illumina for their assistance and expertise with the 450K DNA Methylation array. L.C.L. is supported by an NIH/NICHD K12 Career Development Award and the Hartwell Foundation. G.A., K.L.N., C.L., I.S., F.-J.M., E.F., and J.F.L. are supported by CIRM (CL1-00502, RT1-01108, TR1-01250, RN2-00931-1), NIH (R33MH87925), the Millipore Foundation, and the Esther O'Keefe Foundation. K.L.N. is supported by an Autism Speaks Dennis Weatherstone fellowship. Y.-C.W. is supported by the Marie Mayer Foundation. E.F. was supported by a Bill and Melinda Gates Grand Challenges Explorations Award and a UNCF/Merck Postdoctoral Fellowship. A.L.L. is supported by the Australian Stem Cell Centre, Stem Cells Australia, and the Victoria-California Stem Cell Alliance (CIRM grant TR1-01250). H.S.P. and S.L. were supported by a grant (SC2250) from the Stem Cell Research Center of the 21st Century Frontier Research Program funded by Ministry of Educational Science and Technology. F.-J.M. is supported by an Else-Kr{\"o}ner Fresenius Stiftung fellowship. I.S. is supported by the Pew Charitable Trusts. R.S. is Vice President of International Stem Cell Corporation, from which this study included several parthenogenic human embryonic stem cell lines. ",
year = "2012",
month = may,
day = "4",
doi = "10.1016/j.stem.2012.02.013",
language = "English",
volume = "10",
pages = "620--634",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}