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dc.contributor.authorButcher, Lee Men
dc.contributor.authorIto, Mitsuteruen
dc.contributor.authorBrimpari, Minodoraen
dc.contributor.authorMorris, Tiffany Jen
dc.contributor.authorSoares, Filipa ACen
dc.contributor.authorÄhrlund-Richter, Larsen
dc.contributor.authorCarey, Nessaen
dc.contributor.authorVallier, Ludovicen
dc.contributor.authorFerguson-Smith, Anneen
dc.contributor.authorBeck, Stephanen
dc.identifier.citationButcher et al. Nature Communications (2016) Vol. 7, Article number 10458. doi: 10.1038/ncomms10458en
dc.description.abstractNon-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10−4) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10−6) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.
dc.description.sponsorshipWe thank Kerra Pearce (UCL Genomics) for array processing, and Tim Fell and Jonathan Best (CellCentric), Jason Wray (UCL) and Rosemary Drake (TAP Biosystems) for discussions. We also thank Minal Patel, Chris Kirton, Anja Kolb-Kokocinski, Willem H. Ouwehand, Richard Durbin and Fiona M. Watt on behalf of the Human Induced Pluripotent Stem Cell Initiative (HipSci) funded by grant WT098503 from the Wellcome Trust and the Medical Research Council, for sharing data and materials. This work was supported in part by a TSB/EPSRC grant (TS/H000933/1). The Vallier lab is supported by the Cambridge Hospitals National Institute for Health Research Biomedical Research Center and an ERC Starting Grant (Relieve IMDS). F.A.C.S. is funded by a PhD studentship from Fundação para a Ciência e a Tecnologia (SFRH/BD/69033/2010). The Ferguson-Smith lab is supported by grants from the MRC and Wellcome Trust, and EU-FP7 projects EPIGENESYS (257082) and BLUEPRINT (282510). The Beck lab is supported by the Wellcome Trust (084071), a Royal Society Wolfson Research Merit Award (WM100023), and EU-FP7 projects EPIGENESYS (257082) and BLUEPRINT (282510).
dc.publisherNature Publishing Group
dc.rightsAttribution 2.0 UK: England & Wales*
dc.subjectbiological sciencesen
dc.subjectdevelopmental biologyen
dc.subjectmolecular biologyen
dc.titleNon-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cellsen
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via
prism.publicationNameNature Communicationsen
dc.rioxxterms.funderWellcome Trust
dc.contributor.orcidVallier, Ludovic [0000-0002-3848-2602]
dc.contributor.orcidFerguson-Smith, Anne [0000-0003-4996-9990]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEPSRC (TS/H001220/1)
pubs.funder-project-idMRC (G1000847)
pubs.funder-project-idMRC (MR/J001597/1)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idEC FP7 NOE (282510)
pubs.funder-project-idEC FP7 NOE (257082)
pubs.funder-project-idWellcome Trust (098503/B/12/Z)
pubs.funder-project-idWellcome Trust (095606/Z/11/Z)
pubs.funder-project-idMRC (G0800784)

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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales