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PMID: 21289626 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.

Nature ·Vol. 471 ·No. 7336 ·2011-03-03 ·Pages 68-73

Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O'Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR

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.

MeSH Terms
Cell Differentiation/genetics Cell Line Cellular Reprogramming/genetics CpG Islands/genetics DNA Methylation/genetics Embryonic Stem Cells/cytology,metabolism Epigenomics Epistasis, Genetic/genetics Fibroblasts/cytology,metabolism Genome, Human/genetics Histones/metabolism Humans Induced Pluripotent Stem Cells/cytology,metabolism Trophoblasts/cytology,metabolism
Chemicals
Histones
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Lister Ryan
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Pelizzola Mattia
Kida Yasuyuki S
Hawkins R David
Nery Joseph R
Hon Gary
Antosiewicz-Bourget Jessica
O'Malley Ronan
Castanon Rosa
Klugman Sarit
Downes Michael
Yu Ruth
Stewart Ron
Ren Bing
Thomson James A
Evans Ronald M
Ecker Joseph R
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37 references, click to expand
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature09798
Published
2011-03-03
Epub
2011-00-02
Pages
68-73
Language
English
Region
England
NLM ID
0410462
PMCID
PMC3100360
Subset
IM
Grants
NIDDK NIH HHS · U19 DK062434 · United States
NIEHS NIH HHS · U01 ES017166 · United States
NCI NIH HHS · P30 CA014195 · United States
NIEHS NIH HHS · U01 ES017166-01 · United States
Howard Hughes Medical Institute · United States
Corrections
ErratumIn
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CommentIn
PMID: 21368819
CommentIn
PMID: 21386865
CommentIn
PMID: 21474093
CommentIn
PMID: 21548395
External Links
PubMed source DOI: 10.1038/nature09798 PMC Full Text View journal details
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