Developmental plasticity of epithelial stem cells in tooth and taste bud renewal

Proc Natl Acad Sci U S A. 2019 Sep 3;116(36):17858-17866. doi: 10.1073/pnas.1821202116. Epub 2019 Aug 19.

Abstract

In Lake Malawi cichlids, each tooth is replaced in one-for-one fashion every ∼20 to 50 d, and taste buds (TBs) are continuously renewed as in mammals. These structures are colocalized in the fish mouth and throat, from the point of initiation through adulthood. Here, we found that replacement teeth (RT) share a continuous band of epithelium with adjacent TBs and that both organs coexpress stem cell factors in subsets of label-retaining cells. We used RNA-seq to characterize transcriptomes of RT germs and TB-bearing oral epithelium. Analysis revealed differential usage of developmental pathways in RT compared to TB oral epithelia, as well as a repertoire of genome paralogues expressed complimentarily in each organ. Notably, BMP ligands were expressed in RT but excluded from TBs. Morphant fishes bathed in a BMP chemical antagonist exhibited RT with abrogated shh expression in the inner dental epithelium (IDE) and ectopic expression of calb2 (a TB marker) in these very cells. In the mouse, teeth are located on the jaw margin while TBs and other oral papillae are located on the tongue. Previous study reported that tongue intermolar eminence (IE) oral papillae of Follistatin (a BMP antagonist) mouse mutants exhibited dysmorphic invagination. We used these mutants to demonstrate altered transcriptomes and ectopic expression of dental markers in tongue IE. Our results suggest that vertebrate oral epithelium retains inherent plasticity to form tooth and taste-like cell types, mediated by BMP specification of progenitor cells. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.

Keywords: regeneration; stem cells; taste buds; teeth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation*
  • Cell Plasticity*
  • Cell Self Renewal / genetics
  • Epithelium / metabolism
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Regeneration
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Taste Buds / cytology*
  • Taste Buds / metabolism*
  • Tooth / cytology

Substances

  • Biomarkers