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Updated: Jun 25, 2026

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Published on: September 7, 2017
Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal
Alayne L Brunner1, David S Johnson, Si Wan Kim
1Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
Human embryonic stem cell (hESC) differentiation shows unique DNA methylation patterns, differing from in vivo development. Methyl-seq reveals minimal DNA methylation changes but distinct regulatory region involvement during hESC differentiation.
Area of Science:
- Epigenetics
- Developmental Biology
- Genomics
Background:
- DNA methylation is crucial for cellular differentiation and development.
- Understanding epigenetic regulation in human development is essential.
Purpose of the Study:
- To investigate DNA methylation dynamics during human development using a novel method.
- To compare DNA methylation changes during in vitro human embryonic stem cell (hESC) differentiation and in vivo fetal liver development.
Main Methods:
- Development and application of Methyl-seq, a genome-wide DNA methylation assay covering over 90,000 regions.
- Analysis of DNA methylation patterns in hESCs, their derivatives, and human tissues.
Main Results:
- Differentiation involves DNA methylation changes in a small fraction of assayed regions (2%-11%).
- In vitro hESC differentiation exhibits both de novo methylation and demethylation.
- In vivo fetal liver development is primarily characterized by demethylation.
- hESC differentiation uniquely affects H3K27me3-occupied regions, bivalent domains, and low CpG promoters (LCPs).
- These specific regions become highly unmethylated during in vivo liver development, contrasting with hESC trends.
Conclusions:
- hESC differentiation possesses a distinct DNA methylation signature.
- This signature may not accurately reflect in vivo differentiation processes.
- Specific epigenetic marks and regions are key to understanding differentiation trajectories.
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