# Investigating chemosensory cell heterogeneity in the upper airway epithelium with single cell RNA sequencing and high resolution light sheet microscopy

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $74,402

## Abstract

Project Summary
 The nasal cavity is constantly exposed to airborne particles, some of which are potentially damaging to the
respiratory tract. Noxious particles are trapped in the mucosal layer and are expelled through mucociliary
clearance. Some particles trigger a local, protective inflammatory response through stimulation of solitary
chemosensory cells that results in activation of peptidergic nerve fibers. Solitary chemosensory cells respond
to numerous airborne irritants through receptors on their apical microvillar processes. The range of substances
these cells are known to detect include bitter substances, homoserine lactones excreted by bacteria, and some
odorous irritants. While these cells are generally protective, chronic stimulation could contribute to the etiology
of airway disorders including chronic rhinosinusitis and conductive smell loss. The current proposal seeks to
leverage innovative technologies to explore how this single population of cells is able to detect a wide variety of
airborne irritants. First, single cell RNA-sequencing will be used to examine the heterogeneity of solitary
chemosensory cells. The types of chemoreceptors on individual cells will be investigated and statistical
methods will be used to cluster certain populations of cells based on the transcripts they contain. These results
will help define specific signaling mechanisms by which certain stimuli could activate different classes of
solitary chemosensory cells and signal to the nervous system or surrounding tissue. In the second part of this
proposal, the distribution and innervation of solitary chemosensory cells in the entire nasal cavity will be
explored using optical clearing methods and light sheet microscopy. The use of light sheet microscopy on
optically cleared tissues prevents the need to physically section tissue samples for immunocytochemistry. By
combining these methods, three dimensional reconstructions of large volumes of tissues can be generated to
ascertain accurate spatial information. Specifically, subpopulations of solitary chemosensory cells and nerve
fibers will be visualized using antibodies or RNA-probes. These experiments will address whether certain
populations of solitary chemosensory cells are spatially segregated in the nasal cavity and whether certain
populations are more or less likely to be innervated by peptidergic nerve fibers. The results from this study will
be beneficial to chemosensory and respiratory system scientists. Currently, solitary chemosensory cells are
usually referred to as a homogenous population of chemosensors in the nasal cavity that trigger inflammatory
responses through a single mechanism; however, the results from this study will reshape current knowledge of
solitary chemosensory cells by defining subtypes and examining their distribution patterns within the nose.
These results will give insight to ways that specific stimuli could activate certain classes of solitary
chemosensory cells and communica...

## Key facts

- **NIH application ID:** 10975604
- **Project number:** 7R21DC018864-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Eric D. Larson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $74,402
- **Award type:** 7
- **Project period:** 2020-06-12 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975604

## Citation

> US National Institutes of Health, RePORTER application 10975604, Investigating chemosensory cell heterogeneity in the upper airway epithelium with single cell RNA sequencing and high resolution light sheet microscopy (7R21DC018864-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10975604. Licensed CC0.

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