METTL3-mediated m^(6)A RNA methylation regulates dorsal lingual epithelium homeostasis

The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Alveolar bone is the thickened ridge of jaw bone that supports teeth.It is subject to constant occlusal force and pathogens invasion,and is therefore under active bone remodeling and immunomodulation.Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern.However,a systematic explanation of alveolar bone at single-cell level is still lacking.Here,we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing(scRNA-seq).A more active immune microenvironment is identified in alveolar bone,with a higher proportion of mature immune cells than in long bone.Among all immune cell populations,the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells(MSCs)subpopulation.Alveolar bone monocytes/macrophages express a higher level of Oncostatin M(Osm)compared to long bone,which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs.In summary,our study reveals a unique immune microenvironment of alveolar bone,which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.