English

Researchers from West China School of Stomatology (WCSS), Sichuan University have systematically revealed the epigenetic mechanisms by which injury-induced Ezh2 mediates the spatiotemporal dynamics of H3K27me3 to upstream repress sonic hedgehog (Shh) expression and thus epigenetically decides epithelial adult stem cells (ASCs) fate in vitro and in vivo.  

Identification of injury-induced cell fate alterations and spatiotemporal expression of Shh and H3K27me3 status.

The ASCs residing at the proximal end of rodent incisors can give rise to all cell types of adult dental epithelum, including ameloblast, cementoblast, and odontoblast lineages. The Shh signal hub in adult incisors, located in the transient amplifying (TA) region of epithelium is of great utilization potential in adult enamel regeneration. However, the relationship between epithelial-derived Shh and ASCs fate determination, and the upstream regulatory mechanism of Shh expression remain poorly elucidated. 

In this study, researchers discovered that from homeostasis to injury, the dynamical Ezh2/H3K27me3 signal was involved in ensuring the fidelity of ASCs fate determination via transcriptional inhibition of Shh, and thus maintained the regenerative capacity of mouse incisors.

The findings, published in the journal Science Advances, map the epigenetic mechanisms that control the fidelity of adult dental epithelial stem cells (DESCs) trajectory during incisor homeostasis and regeneration, providing potential targets to improve hard tissue regeneration.

This study was conducted by Professor Ye Ling’s team who have committed to exploring the epigenetic regulation of hard tissue during development and regeneration. The associate professor Fanyuan Yu and postdoctoral fellow Feifei Li are co-first authors, and WCSS is the only signatory unit of the paper. 

For more details of this study, please click the link below.

https://www.science.org/doi/10.1126/sciadv.abn4977