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Olfactory stem cell-mediated regeneration: horizontal basal cell (HBC) lineage [scRNA-seq]

ABSTRACT: The lineage of the horizontal basal cells (HBC) stem cells and their descendants from the olfactory epithelium were profiled by single-cell RNA-Seq to identify differentiated cell types, intermediate stages, transition states, and to infer the lineage trajectories.

ORGANISM(S): Mus musculus

PROVIDER: GSE99251 | GEO | 2017/10/30

SECONDARY ACCESSION(S): PRJNA387707

REPOSITORIES: GEO

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Olfactory stem cell differentiation: horizontal basal cell (HBC) lineage

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Project description:The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic and their relationship to the other specialized epithelial cells, particularly the solitary chemosensory cell family, is unclear. Here, we establish that the family of MVCs comprises tuft cells and ionocytes in both mice and humans. Integrating analysis of the respiratory and olfactory epithelia, we define the unique receptor expression of TRPM5+ tuft-MVCs compared to Gɑ-gustducinhigh 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. Inhalation of Alternaria induced mucosal epithelial effector molecules including Chil4, and a distinct pathway leading to proliferation of the quiescent olfactory horizontal basal stem cell (HBC) pool, both triggered in the absence of olfactory apoptosis. While the Chil4 pathway was dependent on STAT6 signaling and innate lymphocytes, neither were required for HBC proliferation. Alternaria- and ATP- elicited HBC proliferation was dependent on tuft-MVCs, establishing these specialized epithelial cells as regulators of olfactory stem cell responses. Together our data provide high resolution characterization of nasal tuft cell heterogeneity and uncover a novel function for TRPM5+ tuft-MVCs in directing the olfactory mucosal response to allergens.

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