title: Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
abstract: Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.
authors.affiliation: Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Kristopher L
authors.initials: KL
authors.lastname: Nazor
authors.forename: Gulsah
authors.initials: G
authors.lastname: Altun
authors.forename: Candace
authors.initials: C
authors.lastname: Lynch
authors.forename: Ha
authors.initials: H
authors.lastname: Tran
authors.forename: Julie V
authors.initials: JV
authors.lastname: Harness
authors.forename: Ileana
authors.initials: I
authors.lastname: Slavin
authors.forename: Ibon
authors.initials: I
authors.lastname: Garitaonandia
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Müller
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Wang
authors.forename: Francesca S
authors.initials: FS
authors.lastname: Boscolo
authors.forename: Eyitayo
authors.initials: E
authors.lastname: Fakunle
authors.forename: Biljana
authors.initials: B
authors.lastname: Dumevska
authors.forename: Sunray
authors.initials: S
authors.lastname: Lee
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Park
authors.forename: Tsaiwei
authors.initials: T
authors.lastname: Olee
authors.forename: Darryl D
authors.initials: DD
authors.lastname: D'Lima
authors.forename: Ruslan
authors.initials: R
authors.lastname: Semechkin
authors.forename: Mana M
authors.initials: MM
authors.lastname: Parast
authors.forename: Vasiliy
authors.initials: V
authors.lastname: Galat
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Laslett
authors.forename: Uli
authors.initials: U
authors.lastname: Schmidt
authors.forename: Hans S
authors.initials: HS
authors.lastname: Keirstead
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Loring
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D019175:DNA Methylation; D014644:Genetic Variation; D018392:Genomic Imprinting; D006801:Humans; D009928:Organ Specificity; D039904:Pluripotent Stem Cells / Q000502:physiology*; D012008:Recurrence; D055153:Stem Cell Niche; D049951:X Chromosome Inactivation