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Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells

Butcher, LM; Ito, M; Brimpari, M; Morris, TJ; Soares, FA; Ährlund-Richter, L; Carey, N; ... Beck, S; + view all (2016) Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells. Nature Communications , 7 , Article 10458. 10.1038/ncomms10458. Green open access

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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.

Type: Article
Title: Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms10458
Publisher version: http://dx.doi.org/10.1038/ncomms10458
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Biological sciences; Developmental biology; Molecular biology
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: http://discovery.ucl.ac.uk/id/eprint/1475608
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