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Updated: Jun 4, 2025
11:53
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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NSD3 protein methylation and stabilization transforms human ES cells into variant state.
Vignesh K Krishnamoorthy1,2, Fariha Hamdani1, Pooja Shukla1
1https://ror.org/05ef28661 Council of Scientific and Industrial Research (CSIR) - Institute of Genomics and Integrative Biology (IGIB), New Delhi, India.
Life Science Alliance
|December 31, 2024
Summary
Human embryonic stem cells (hESCs) can become cancerous. This study found that misregulating the NSD3 protein, through methylation, causes hESCs to transform into cancer cells.
Area of Science:
- Stem cell biology
- Cancer research
- Epigenetics
Background:
- Cultured human embryonic stem cells (hESCs) are prone to genetic anomalies.
- These anomalies can lead to cellular transformation and increased cancer susceptibility.
Purpose of the Study:
- To characterize a variant hESC (vhESC) line.
- To investigate the molecular mechanisms driving hESC transformation.
Main Methods:
- Characterization of vhESC line.
- Analysis of epigenomic landscape and protein expression.
- Gene depletion studies (NSD3, EHMT2).
- Methylation site identification (NSD3 K477).
Main Results:
- vhESCs exhibit upregulated EMT markers, accelerated wound healing, and compromised differentiation.
- Altered epigenomic landscape and overexpression of EHMT1, EHMT2, and NSD proteins observed in vhESCs.
- Depletion of NSD3 reversed transformation phenotypes.
- EHMT2 methylates NSD3 at K477, stabilizing its protein levels and abrogating degradation in hESCs.
Conclusions:
- Misregulation of NSD3, via methylation-induced stabilization, drives oncogenic transformation in hESCs.
- This provides a novel mechanism linking epigenetics and cancer development in pluripotent stem cells.
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