Genome-Wide Demethylation by 5-aza-2’-Deoxycytidine Alters the Cell Fate of Stem/Progenitor Cells
- 503 Downloads
DNA methyltransferase (DNMT) inhibitor 5-aza-2’-deoxycytidine (5-aza-CdR) is able to cause DNA demethylation in the genome and induce the expression of silenced genes. Whether DNA demethylation can affect the gene expression of stem/progenitor cells has not been understood. Mouse utricle epithelia-derived progenitor cells (MUCs), which possess stem cell features as previously described, exhibit a potential DNA methylation status in the genome. In this study, MUCs were treated with 5-aza-CdR to determine whether DNMT inhibitor is able to induce the differentiation of MUCs. With 5-aza-CdR treatment for 72 hr, MUCs expressed epithelial genes including Cdh1, Krt8, Krt18, and Dsp. Further, hair cell genes Myo7a and Myo6 increased their expressions in response to 5-aza-CdR treatment. The decrease in the global methylated DNA values after 5-aza-CdR treatment indicated a significant DNA demethylation in the genome of MUCs, which may contribute to remarkably increased expression of epithelial genes and hair cell genes. The progenitor MUCs then turned into an epithelial-like hair cell fate with the expression of both epithelial and hair cell genes. This study suggests that stem cell differentiation can be stimulated by DNA demethylation, which may open avenues for studying stem cell fate induction using epigenetic approaches.
Keywords5-aza-2’-deoxycytidine Demethylation Epigenetics Epithelial Hair cell Methylation Prosensory cell Stem cell
The authors thank Neelkumar Patel for his technical support and Jue Wang, Fei Nei, and Xiaoyang Li for valuable comments to the manuscript. The study is supported by NIDCD/NIH (1 R01 DC013275) and the Grants Plus Program from the Wayne State University.
Conflict of Interest
The authors indicate no potential conflicts of interest.
- 23.Ghoshal, K., Datta, J., Majumder, S., et al. (2005). 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Molecular and Cellular Biology, 25(11), 4727–4741.CrossRefPubMedCentralPubMedGoogle Scholar
- 26.Phillips, T. (2008). The role of methylation in gene expression. Nature Education, 1(1), 116.Google Scholar