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Updated: Apr 26, 2026
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An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
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Dynamic heterogeneity and DNA methylation in embryonic stem cells
Zakary S Singer1, John Yong2, Julia Tischler3
1Computation and Neural Systems, California Institute of Technology, Pasadena, CA 91125, USA.
Molecular Cell
|July 20, 2014
Summary
Embryonic stem cells (ESCs) switch between gene expression states due to intrinsic noise and epigenetic regulation. The "2i" pathway influences these dynamics, revealing mechanisms of cellular heterogeneity.
Area of Science:
- * Molecular biology
- * Developmental biology
- * Epigenetics
Background:
- * Cellular heterogeneity arises from multiple states and gene expression noise.
- * Disentangling these variability sources is crucial for understanding cell dynamics.
- * Embryonic stem cells (ESCs) exhibit dynamic regulatory factor expression, making them ideal models.
Purpose of the Study:
- * To differentiate stochastic noise from coherent gene expression states in individual ESCs.
- * To investigate the role of the
- pathway inhibitors in modulating cellular variability.
- * To elucidate the contribution of DNA methylation to maintaining ESC metastable states.
Main Methods:
- * Single-molecule RNA-fluorescence in situ hybridization (RNA-FISH).
- * Quantitative time-lapse microscopy of individual ESCs.
- * Analysis of gene expression dynamics and variability.
Main Results:
- * Identified stochastic switching between two coherent gene expression states.
- * Characterized burst-like transcriptional noise.
- * Demonstrated that
- pathway inhibitors modulate both noise and state switching.
- * Found DNA methylation is critical for maintaining metastable states.
Conclusions:
- * ESC gene expression arises from intrinsic noise, coherent states, and epigenetic regulation.
- * The
- pathway influences ESC dynamics.
- * DNA methylation stabilizes ESC gene expression states.
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