Single-cell RNA-sequencing analysis of mouse circumvallate papilla reveals a role for Notch signaling in taste cell fate decisions

Oral presentation

Dany Gaillard ¹, Eric Larson ², Lauren Shechtman ¹, Trevor Isner ^{1, 3}, Jennifer Scott ¹, Theresa Keeley ⁴, Austin Gillen ⁵, Peter Dempsey ⁶, Linda Samuelson ⁴, Linda Barlow ^{1, 3}

¹ Department of Cell & Developmental Biology, and the Rocky Mountain Taste & Smell Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, ² Department of Otolaryngology, and the Rocky Mountain Taste & Smell Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, ³ Cell Biology, Stem Cells and Development graduate program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, ⁴ Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA, ⁵ RNA Bioscience Initiative Bioinformatics Fellows, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, ⁶ Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Taste buds are composed of functionally heterogeneous taste bud cells (TBCs) that transduce sweet, sour, salt, umami, and bitter stimuli. In addition, each bud houses a large proportion of glial-like support cells, i.e., Type I TBCs. All TBCs continually renew from adult lingual stem cells that also produce the non-taste epithelium of tongue; however, the lineage relationships of these cell types, as well as factors that regulate acquisition of these many distinct cell fates are largely unexplored. We have used analysis of single cell transcriptome data of adult mouse circumvallate taste papilla to identify stem populations and the subsequent lineage steps that lead to production of taste and non-taste epithelial cell types. Now, we employ CellChat (http://www.cellchat.org/) to bioinformatically identify active signaling pathways and the polarity of signaling for specific lineage steps, i.e., ligand-expressing signaling cells and receptor-expressing cell populations. This analysis confirms and expands our understanding of WNT and Hedgehog signaling in taste homeostasis, and identifies a host of new candidate regulatory pathways that likely control different aspects of taste bud cell renewal. In particular, CellChat analysis suggests that Notch signaling functions iteratively in taste epithelium to (1) regulate lingual stem cells and (2) drive differentiation of Type I TBCs. We are testing these hypotheses of Notch function in vivo using molecular genetic mouse models to activate Notch signaling at distinct lineage steps, and in vitro, treating lingual organoids derived from adult taste stem cells with small molecule Notch pathway inhibitors and activators.