# Label-retaining globose basal cells as neurocompetent stem cells of the olfactory epithelium

> **NIH NIH F30** · TUFTS UNIVERSITY BOSTON · 2021 · $51,036

## Abstract

Project Summary
 The olfactory epithelium (OE) is chemosensory neuroepithelium lining the posterodorsal surface of the
nasal cavity. This neuroepithelium is exceptional in its ability to provide constitutive neurogenesis and
regenerate in bulk after injury. Despite the well-documented regenerative capacity of the OE, anosmia is
reported in the majority of individuals over the age of 65 and has negative implications for quality of life,
nutritional status, and safety. Histology of aged, anosmic human OE has revealed a loss of not only olfactory
sensory neurons (OSNs) but the globose basal stem and progenitor cells that produce them. In this way, age-
deponent olfactory neuropathology is the direct consequence of a failure in long-term tissue homeostasis
attributable to exhaustion of neural stem cells.
 GBCs were historically recognized as a heterogeneous population of “active” neural stem and
progenitor cells that are exceptional in their ability to provide constitutive OSN replacement and bulk
regeneration, dynamically responding to the status of the epithelium. Recently a rare, quiescent subtype of
GBC was discovered that retains thymidine labels, activates to contribute to post-injury regeneration via an
unknown mechanism, and re-enters into quiescence after regeneration. These label-retaining GBCs (LR-
GBCs) are analogous to other label-retaining cells observed, but poorly understood, in a number of epithelial
tissues.
 The proposed aims seek to develop a mechanistic and molecular understanding of the regulation of
LR-GBCs by leveraging the strengths of olfactory epithelium injury models and single-cell transcriptomics. The
proliferation and potency of canonical GBCs are enhanced to repopulate the wounded epithelium when mature
OSNs are selectively ablated, therefore it bears specifically testing whether LR-GBCs are regulated in a similar
fashion. This proposal will investigate the overarching hypothesis that mature olfactory sensory
neurons regulate the activation and quiescence of label-retaining GBCs, with the long-term goal of
understanding how neural stem cells contribute to age-dependent neuropathology. This will be accomplished
by answering the following three questions:
 Aim 1 — Is a selective loss of mature OSNs sufficient for activating LR-GBCs?
 Aim 2 — Are mature OSNs necessary for re-establishing LR-GBCs after injury
 Aim 3 — What genetic programs are activated in LR-GBCs during the acute injury response?

## Key facts

- **NIH application ID:** 10148755
- **Project number:** 5F30DC017354-04
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Matthew Zunitch
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2018-05-16 → 2022-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148755

## Citation

> US National Institutes of Health, RePORTER application 10148755, Label-retaining globose basal cells as neurocompetent stem cells of the olfactory epithelium (5F30DC017354-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10148755. Licensed CC0.

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