Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells

Ryan Lister, Mattia Pelizzola, Yasuyuki S. Kida, R. David Hawkins, Joseph R. Nery, Gary Hon, Jessica Antosiewicz-Bourget, Ronan Ogmalley, Rosa Castanon, Sarit Klugman, Michael Downes, Ruth Yu, Ron Stewart, Bing Ren, James A. Thomson, Ronald M. Evans, Joseph R. Ecker

Research output: Contribution to journalArticle

1069 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)68-73
Number of pages6
JournalNature
Volume471
Issue number7336
DOIs
StatePublished - Mar 3 2011

ASJC Scopus subject areas

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    Lister, R., Pelizzola, M., Kida, Y. S., Hawkins, R. D., Nery, J. R., Hon, G., Antosiewicz-Bourget, J., Ogmalley, R., Castanon, R., Klugman, S., Downes, M., Yu, R., Stewart, R., Ren, B., Thomson, J. A., Evans, R. M., & Ecker, J. R. (2011). Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature, 471(7336), 68-73. https://doi.org/10.1038/nature09798