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Updated: Aug 13, 2025
09:04
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
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DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells.
Andrea Lauria1,2, Guohua Meng1,2, Valentina Proserpio1,2
1Department of Life Sciences and Systems Biology & Molecular Biotechnology Center - MBC, Università di Torino, Via Nizza 52, 10126, Torino, Italy.
Nature Communications
|January 23, 2023
Summary
DNA methyltransferase 3B (DNMT3B) establishes DNA methylation patterns in epiblast-like cells, crucial for proper cell fate specification. Its absence impairs meso-endodermal differentiation, highlighting DNMT3B
Area of Science:
- Epigenetics and Developmental Biology
- Genomics and Molecular Biology
Background:
- Proper DNA methylation is critical for cell fate determination during early development.
- The precise mechanisms and targets of de novo DNA methylation during differentiation remain incompletely understood.
Purpose of the Study:
- To investigate the role of DNMT3B in DNA methylation during mouse early development.
- To identify DNMT3B-dependent regulatory elements and their impact on cell fate decisions.
Main Methods:
- In vitro stem cell differentiation models.
- Loss-of-function experiments (Dnmt3b knockout).
- High-throughput genome-wide bisulfite sequencing, bulk and single-cell RNA sequencing.
Main Results:
- DNMT3B-dependent DNA methylation in epiblast-like cells (EpiLCs) primes developmental trajectories.
- Dnmt3b knockout impairs meso-endodermal progenitor differentiation and promotes neuro-ectodermal lineage commitment.
- DNMT3B re-establishes Sox2 super-enhancer methylation, downregulates Sox2, and restores meso-endodermal markers.
Conclusions:
- DNMT3B-mediated DNA methylation at the epiblast stage is essential for priming meso-endodermal lineages.
- This study functionally characterizes de novo DNA methyltransferases in EpiLC lineage determination.
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