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Published on: June 1, 2018
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Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells
Lee M Butcher1,2, Mitsuteru Ito3, Minodora Brimpari4
1UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
Nature Communications
|January 30, 2016
Summary
Reduced non-CG methylation in pluripotent stem cells impairs endodermal differentiation. A novel biomarker using nine non-CG sites accurately predicts this differentiation capacity in human induced pluripotent stem cells and human embryonic stem cells.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Developmental Biology
Background:
- Non-CpG (non-CG) methylation is an epigenetic mark in pluripotent stem cells.
- Its role in differentiation, particularly into endodermal lineages, remains largely unexplored.
Purpose of the Study:
- To investigate the association between non-CG methylation and endodermal differentiation capacity in human pluripotent stem cells.
- To identify potential non-CG methylation biomarkers for predicting differentiation potential.
Main Methods:
- Genome-wide analysis of 2,670 non-CG sites in 25 human induced pluripotent stem cell (hiPSC) lines.
- Validation of a simplified assay using nine non-CG sites in an independent cohort of hiPSCs and human embryonic stem cell (hESC) lines.
Main Results:
- A significant, unidirectional loss of non-CG methylation was observed, correlating with impaired endodermal differentiation capacity (92% accuracy in discovery cohort).
- The simplified nine-site assay maintained high predictive power (23% Δβ, P<9.1 × 10(-6)) and correctly identified differentiation capacity in 90% of lines in the replication cohort.
Conclusions:
- Non-CG methylation patterns, particularly at specific sites, serve as a reliable biomarker for assessing endodermal differentiation capacity.
- This finding has implications for stem cell research and therapeutic applications requiring controlled differentiation.
