m6A-Modified GATA2 Enhances Odontogenic Differentiation in Stem Cells from the Apical Papilla
Year: 2025
Type: article
Abstract: Epigenetic modifications play a crucial role in regulating stem cell differentiation. Among these, N6-methyladenosine (m6A) modification significantly impacts mRNA stability and translation. However, its role in dental stem cell differentiation remains largely unexplored. Functional assays, including ALP activity, alizarin red S staining, qPCR, and Western blot, were conducted to assess odontogenic differentiation. Then, an in vivo dentin formation model was used to validate our findings. Additionally, we employed RNA stability assays and m6A site mutagenesis to investigate the regulatory mechanism of m6A modification in GATA2-mediated differentiation. Our results demonstrated that overexpression of GATA2 significantly promoted SCAP odontogenic differentiation. Moreover, in vivo studies confirmed that GATA2 overexpression enhances dentin formation in mouse models. Conversely, knockdown of GATA2 or mutation of its m6A sites led to reduced mRNA stability and decreased odontogenic differentiation. m6A modification is enriched in the 3′ untranslated region (3′UTR) of GATA2 mRNA, regulating its stability and expression. Our findings indicate that m6A modification contributes to the post-transcriptional regulation of GATA2, enhancing its stability and promoting SCAP-mediated odontogenic differentiation and dentin formation. This study provides new insights into the epigenetic regulation of dental stem cells and suggests a potential molecular target for dental tissue regeneration.
DOI: 10.3390/ijms26072920
Authors: Haoqing Yang, Fengning Yuan, Jiaxin Song, Yishu Huang, Zhaochen Shan, Zhipeng Fan
Institution: Capital Medical University
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4408776186