2011 March 3 | Ryan Lister¹,², Mattia Pelizzola¹,², Yasuyuki S. Kida¹,², R. David Hawkins³, Joseph R. Nery¹, Gary Hon¹, Jessica Antosiewicz-Bourget⁴,⁵, Ronan O'Malley², Rosa Castanon¹, Sarit Klugman³, Michael Downes², Ruth Yu², Ron Stewart⁴,⁵, Bing Ren³,⁶, James A. Thomson⁴,⁵,⁷,⁸, Ronald M. Evans², and Joseph R. Ecker¹
A study published in Nature (2011) investigates the epigenomic reprogramming of human induced pluripotent stem cells (iPSCs). The research reveals that while iPSCs generally resemble embryonic stem (ES) cells in DNA methylation patterns, significant variability exists between different iPSC lines. This variability includes somatic memory, where residual methylation patterns from the original somatic cell persist, and iPSC-specific differentially methylated regions (DMRs). The study also identifies megabase-scale regions of aberrant non-CG methylation near centromeres and telomeres, which are not fully reprogrammed to an ES-cell-like state. These regions are associated with altered histone modifications and gene expression. Furthermore, errors in CG methylation reprogramming are transmitted to differentiated cells, indicating that the reprogramming process is not fully reversible. The findings highlight the importance of comprehensive epigenomic profiling in understanding the reprogramming process and its implications for iPSC use in regenerative medicine and disease research. The study underscores the need for further investigation into the mechanisms underlying these epigenetic differences and their potential impact on iPSC functionality and application.A study published in Nature (2011) investigates the epigenomic reprogramming of human induced pluripotent stem cells (iPSCs). The research reveals that while iPSCs generally resemble embryonic stem (ES) cells in DNA methylation patterns, significant variability exists between different iPSC lines. This variability includes somatic memory, where residual methylation patterns from the original somatic cell persist, and iPSC-specific differentially methylated regions (DMRs). The study also identifies megabase-scale regions of aberrant non-CG methylation near centromeres and telomeres, which are not fully reprogrammed to an ES-cell-like state. These regions are associated with altered histone modifications and gene expression. Furthermore, errors in CG methylation reprogramming are transmitted to differentiated cells, indicating that the reprogramming process is not fully reversible. The findings highlight the importance of comprehensive epigenomic profiling in understanding the reprogramming process and its implications for iPSC use in regenerative medicine and disease research. The study underscores the need for further investigation into the mechanisms underlying these epigenetic differences and their potential impact on iPSC functionality and application.