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.
authors.affiliation: Department of Ob/Gyn and Center for Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohi
authors.forename: Han
authors.initials: H
authors.lastname: Qin
authors.forename: Chibo
authors.initials: C
authors.lastname: Hong
authors.forename: Laure
authors.initials: L
authors.lastname: Blouin
authors.forename: Jose M
authors.initials: JM
authors.lastname: Polo
authors.forename: Tingxia
authors.initials: T
authors.lastname: Guo
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Qi
authors.forename: Sara L
authors.initials: SL
authors.lastname: Downey
authors.forename: Philip D
authors.initials: PD
authors.lastname: Manos
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Rossi
authors.forename: Jingwei
authors.initials: J
authors.lastname: Yu
authors.forename: Matthias
authors.initials: M
authors.lastname: Hebrok
authors.forename: Konrad
authors.initials: K
authors.lastname: Hochedlinger
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.forename: Jun S
authors.initials: JS
authors.lastname: Song
authors.forename: Miguel
authors.initials: M
authors.lastname: Ramalho-Santos
mesh_terms: D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic