@article{cf9509a11ce04fa88fd77d79d3a2c248,
title = "Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells",
abstract = "Human induced pluripotent stem (iPS) cells are remarkably similar to embryonic stem (ES) cells, but recent reports indicate that there may be important differences between them. We carried out a systematic comparison of human iPS cells generated from hepatocytes (representative of endoderm), skin fibroblasts (mesoderm) and melanocytes (ectoderm). All low-passage iPS cells analysed retain a transcriptional memory of the original cells. The persistent expression of somatic genes can be partially explained by incomplete promoter DNA methylation. This epigenetic mechanism underlies a robust form of memory that can be found in iPS cells generated by multiple laboratories using different methods, including RNA transfection. Incompletely silenced genes tend to be isolated from other genes that are repressed during reprogramming, indicating that recruitment of the silencing machinery may be inefficient at isolated genes. Knockdown of the incompletely reprogrammed gene C9orf64 (chromosome 9 open reading frame 64) reduces the efficiency of human iPS cell generation, indicating that somatic memory genes may be functionally relevant during reprogramming.",
author = "Yuki Ohi and Han Qin and Chibo Hong and Laure Blouin and Polo, {Jose M.} and Tingxia Guo and Zhongxia Qi and Downey, {Sara L.} and Manos, {Philip D.} and Rossi, {Derrick J.} and Jingwei Yu and Matthias Hebrok and Konrad Hochedlinger and Costello, {Joseph F.} and Song, {Jun S.} and Miguel Ramalho-Santos",
note = "Funding Information: The authors wish to thank S. Fisher, O. Genbachev, A. Leavitt and B. Conklin for expert advice on culturing human ES cells, D. Subramanyam and R. Blelloch for the Adult Fibroblast-iPS 1 cell line, L. Ta, A. Williams and A. Holloway at the Gladstone Institutes, J. Bolen at the Mouse Pathology Core Facility for expert assistance, J. Utikal for technical advice, and J. Yang and A. Campain for sharing their meta-DEDS code. We thank members of the Santos laboratory, R. Blelloch, H. Willenbring, S. Fisher and M. Grskovic for helpful discussions and critical reading of the manuscript. Work in the Santos laboratory is supported by CIRM, JDRF, an NIH Director{\textquoteright}s New Innovator Award and the Leona M. and Harry B. Helmsley Charitable Trust. Y.O. was partially supported by the UCSF Diabetes Center and a T32 grant from the NICHD to the UCSF Center for Reproductive Sciences. Work in M.H.{\textquoteright}s laboratory was supported by grants from the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust. T.G. was supported by the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust. S.L.D. was partially supported by CIRM. J.S.S. was partially supported by the PhRMA Foundation.",
year = "2011",
month = may,
doi = "10.1038/ncb2239",
language = "English (US)",
volume = "13",
pages = "541--549",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "5",
}