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Updated: May 20, 2026

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency
Published on: June 10, 2018
Epigenetic stability, adaptability, and reversibility in human embryonic stem cells.
Joshua D Tompkins1, Christine Hall, Vincent Chang-yi Chen
1Department of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Human embryonic stem cells (hESCs) exhibit a memory of their culture history, with some gene expression and DNA methylation changes persisting even after returning to original conditions.
Area of Science:
- Stem Cell Biology
- Epigenetics
- Genomics
Background:
- Human embryonic stem cell (hESC) stability is crucial for research and clinical use.
- Culture conditions significantly impact hESC behavior and stability.
- Understanding hESC adaptation and memory is key to reliable stem cell applications.
Purpose of the Study:
- To investigate the stability of hESCs under different culture conditions.
- To determine if hESCs retain a memory of their culture history.
- To explore the epigenetic and transcriptional changes associated with hESC adaptation.
Main Methods:
- Comparative analysis of gene transcription profiles.
- DNA methylation profiling under varying culture conditions.
- Assessment of reversibility of epigenetic and transcriptional changes upon culture reversion.
Main Results:
- hESCs undergo significant transcriptional and DNA methylation changes in response to new culture environments.
- While many changes are reversible upon returning to original conditions, some transcriptional and DNA methylation alterations persist, indicating a culture history memory.
- An inverse correlation was observed between hypomethylation upstream of promoters and gene expression.
- G-protein coupled receptor pathway regulation partially explains observed transcriptional shifts.
Conclusions:
- hESCs possess a memory of their culture history, influencing their epigenetic and transcriptional states.
- The plasticity of DNA methylation is high, but some changes are persistent.
- Understanding this memory is vital for standardizing hESC culture for therapeutic and research purposes.
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