title: Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.
abstract: Non-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.
authors.affiliation: UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.|Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Butcher
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Ito
authors.affiliation: Anne McLaren Laboratory, Department of Surgery, Wellcome Trust and Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK.
authors.forename: Minodora
authors.initials: M
authors.lastname: Brimpari
authors.affiliation: UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.|Cambridge Epigenetix, Jonas Webb Building, Babraham Campus, Cambridge CB22 3AT, UK.
authors.forename: Tiffany J
authors.initials: TJ
authors.lastname: Morris
authors.affiliation: Anne McLaren Laboratory, Department of Surgery, Wellcome Trust and Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK.|Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
authors.forename: Filipa A C
authors.initials: FAC
authors.lastname: Soares
authors.affiliation: Division of Paediatric Oncology, Department of Women's and Children's Health, Karolinska Institutet,171 76 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Ährlund-Richter
authors.affiliation: PraxisUnico, The Jeffreys Building, St John's Innovation Park, Cambridge CB4 0DE, UK.
authors.forename: Nessa
authors.initials: N
authors.lastname: Carey
authors.affiliation: Anne McLaren Laboratory, Department of Surgery, Wellcome Trust and Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK.|Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Vallier
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.affiliation: UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D015331:Cohort Studies; D019175:DNA Methylation; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers
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