@article{977596ed21224825acbd045b65bba062,
title = "Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells",
abstract = "Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.",
author = "Ryan Lister and Mattia Pelizzola and Kida, {Yasuyuki S.} and Hawkins, {R. David} and Nery, {Joseph R.} and Gary Hon and Jessica Antosiewicz-Bourget and Ronan Ogmalley and Rosa Castanon and Sarit Klugman and Michael Downes and Ruth Yu and Ron Stewart and Bing Ren and Thomson, {James A.} and Evans, {Ronald M.} and Ecker, {Joseph R.}",
note = "Funding Information: Acknowledgements We thank L. Zhang and G. Schroth for assistance with MethylC-Seq library sequencing. R.L. is supported by a California Institute for Regenerative Medicine Training Grant. M.P. is supported by a Catharina Foundation postdoctoral fellowship. R.D.H. is supported by an American Cancer Society Postdoctoral Fellowship. Y.K. is supported by the Japan Society for the Promotion of Science. This work was supported by grants from the following: Mary K. Chapman Foundation, the National Science Foundation (NSF) (NSF 0726408), the National Institutes of Health (NIH) (U01 ES017166, U01 1U01ES017166-01, DK062434), the California Institute for Regenerative Medicine (RB2-01530), the Morgridge Institute for Research and the Howard Hughes Medical Institute. We thank the NIH Roadmap Reference Epigenome Consortium (http://www.roadmapepigenomics.org/). This study was carried out as part of the NIH Roadmap Epigenomics Program.",
year = "2011",
month = mar,
day = "3",
doi = "10.1038/nature09798",
language = "English (US)",
volume = "471",
pages = "68--73",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7336",
}