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Knockdown H19 Accelerated iPSCs Reprogramming through Epigenetic Modifications and Mesenchymal-to-Epithelial
Ruizhen Sun1, Ximei Zhang1, Tiantian Gong1
1Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Biomolecules
|May 24, 2024
Summary
The imprinted gene H19 acts as a barrier during induced pluripotent stem cell (iPSC) reprogramming. Reducing H19 expression enhances reprogramming efficiency and promotes pluripotency gene activation.
Area of Science:
- Developmental Biology
- Epigenetics
- Stem Cell Biology
Background:
- H19 is an essential imprinted gene crucial for embryonic development.
- Reprogramming processes involve complex epigenetic changes and asymmetric pronuclear capacities.
- The role of H19 in induced pluripotent stem cell (iPSC) reprogramming remains largely unexplored.
Purpose of the Study:
- To investigate the function of H19 during the iPSC reprogramming process.
- To determine how H19 influences reprogramming efficiency and epigenetic patterns.
- To elucidate the role of H19 as a potential barrier in early reprogramming.
Main Methods:
- Analysis of H19 expression during iPSC reprogramming.
- Assessment of reprogramming efficiency following H19 knockdown.
- Bisulfite genomic sequencing to analyze Oct4 promoter methylation.
- Gene expression analysis of pluripotency and epithelial-to-mesenchymal transition (EMT) markers.
Main Results:
- H19 expression transiently increased during iPSC reprogramming.
- H19 knockdown significantly improved reprogramming efficiency.
- Pluripotency gene expression was enhanced, and the Oct4 promoter was demethylated in H19 knockdown cells.
- Mesenchymal regulators of EMT were downregulated upon H19 knockdown during reprogramming.
Conclusions:
- H19 acts as a barrier to early iPSC reprogramming.
- Modulating H19 expression can enhance reprogramming efficiency.
- These findings offer functional insights into H19's role in epigenetic regulation during cell reprogramming.
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