| Autor: |
Saltanat Ualiyeva, Evan Lemire, Caitlin Wong, Amelia Boyd, Evelyn C. Avilés, Dante G. Minichetti, Alexander Perniss, Alice Maxfield, Rachel Roditi, Ichiro Matsumoto, Nora A. Barrett, Kathleen M. Buchheit, Tanya M. Laidlaw, Joshua A. Boyce, Lora G. Bankova, Adam L Haber |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.09.26.509561 |
| Popis: |
The olfactory neuroepithelium serves as a sensory organ for odors and is part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. A subset of these, microvillous cells (MVCs), are strategically positioned at the apical surface but their specific functions are still enigmatic and their relationship to the rest of the solitary chemosensory cell family is unclear. Here, we establish that the larger family of MVCs comprises tuft cells and ionocytes in both mice and humans. Olfactory TRPM5+tuft-MVCs share a core transcriptional profile with the chemosensory tuft family, prominently including the machinery for lipid mediator generation. Integrating analysis of the respiratory and olfactory epithelium, we define the unique receptor expression of TRPM5+tuft-MVC compared to the Gɑ-gustducin+respiratory tuft cells and characterize a new population of glandular DCLK1+tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we employed an integrated single-cell transcriptional and protein analysis. We defined a remodeling olfactory epithelial switch pathway with induction ofChil4and a distinct pathway of proliferation of the quiescent olfactory horizontal basal stem cell (HBC), both triggered in the absence of significant olfactory apoptosis. While theChil4pathway was dependent on STAT6 signaling and innate lymphocytes, neither were required for HBC proliferation. HBC proliferation was dependent on tuft-MVCs, establishing these specialized epithelial cells as both sensors for allergens and regulators of olfactory stem cell responses. Together our data provide high resolution characterization of the nasal tuft cell heterogeneity and uncover a novel mechanism by which TRPM5+tuft cells direct the olfactory mucosal response to allergens.One Sentence SummaryWe identify the enigmatic TRPM5+olfactory microvillous cells as tuft cells, and show their functional role as regulators of olfactory stem cell proliferation in response to environmental signals. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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