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 O’Malley, Rosa Castanon, Sarit Klugman, Michael Downes, Ruth Yu, Ron Stewart, Bing Ren, James A. Thomson, Ronald M. Evans and Joseph R. Ecker ()
Additional contact information
Ryan Lister: Genomic Analysis Laboratory, The Salk Institute for Biological Studies
Mattia Pelizzola: Genomic Analysis Laboratory, The Salk Institute for Biological Studies
Yasuyuki S. Kida: Howard Hughes Medical Institute, Gene Expression laboratory, The Salk Institute for Biological Studies
R. David Hawkins: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Joseph R. Nery: Genomic Analysis Laboratory, The Salk Institute for Biological Studies
Gary Hon: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Jessica Antosiewicz-Bourget: Morgridge Institute for Research
Ronan O’Malley: Genomic Analysis Laboratory, The Salk Institute for Biological Studies
Rosa Castanon: Genomic Analysis Laboratory, The Salk Institute for Biological Studies
Sarit Klugman: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Michael Downes: Howard Hughes Medical Institute, Gene Expression laboratory, The Salk Institute for Biological Studies
Ruth Yu: Howard Hughes Medical Institute, Gene Expression laboratory, The Salk Institute for Biological Studies
Ron Stewart: Morgridge Institute for Research
Bing Ren: Ludwig Institute for Cancer Research, 9500 Gilman Drive
James A. Thomson: Morgridge Institute for Research
Ronald M. Evans: Howard Hughes Medical Institute, Gene Expression laboratory, The Salk Institute for Biological Studies
Joseph R. Ecker: Genomic Analysis Laboratory, The Salk Institute for Biological Studies

Nature, 2011, vol. 471, issue 7336, 68-73

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature09798

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