Lrig1 -expressing quiescent stem cells maintain vocal fold mucosal homeostasis via Notch signaling Article Swipe
Vlasta Lungova
,
Jessica M. Fernandez
,
Yu-Jia Cai
,
Christina Kendziorski
,
Susan L Thibeault
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2513590122
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2513590122
Identifying progenitor cells in laryngeal and vocal fold (VF) mucosa is essential for advancing stem cell–based therapies for VF diseases. In this study, we used Lrig1 (leucine-rich repeats and immunoglobulin-like domains 1) gene to label tissue-resident stem cells within laryngeal and VF mucosa, aiming to investigate cellular networks underlying VF homeostasis and regeneration. Lrig1 + cells exhibited hallmark features of quiescent stem cells—including slow cycling, long-term persistence, and differentiation potential—and contributed to sustained VF regeneration and repair after naphthalene injury. By one week post injury Lrig1 + progeny restored the damaged VF epithelium. Transcriptionally, these cells suppressed cell type specific genes and proliferation while activating programs related to RNA metabolism, epigenetic regulation, and protein ubiquitination, consistent with quiescence and readiness for activation. Lrig1 + cells were enriched in basal, parabasal, and immature secretory populations within surface epithelium and submucosal glands, residing in niches characterized by transcriptional flexibility and spatial shielding from direct stress—features that likely prevent premature or chronic mobilization. Notably, analogous LRIG1 expressing cells were identified in human laryngeal and VF tissues, highlighting the translational relevance of our findings. To explore regulation of Lrig1 + cell quiescence, we conditionally deleted Notch1, which led to epithelial hyperplasia, expansion of secretory populations, and mucus hyperproduction. In summary, Lrig1 marks a conserved, quiescent stem cell population in the larynx and VFs that supports long-term tissue homeostasis and repair, with quiescence maintained via Notch1 signaling.
Related Topics
Concepts
Stem cell
Cell biology
Biology
Progenitor cell
Homeostasis
Population
Regeneration (biology)
Epithelium
Adult stem cell
Wnt signaling pathway
Epigenetics
Cell
Immunology
Larynx
Amniotic epithelial cells
Mucus
Progenitor
Cell type
Cellular differentiation
Transcriptome
Gene
Tight junction
Vocal folds
Regulation of gene expression
Gene expression
Cell culture
Notch signaling pathway
Respiratory epithelium
Side population
Somatic cell
Pathology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2513590122
- OA Status
- hybrid
- References
- 34
- OpenAlex ID
- https://openalex.org/W7106623389
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W7106623389Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1073/pnas.2513590122Digital Object Identifier
- Title
-
Lrig1 -expressing quiescent stem cells maintain vocal fold mucosal homeostasis via Notch signalingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-11-25Full publication date if available
- Authors
-
Vlasta Lungova, Jessica M. Fernandez, Yu-Jia Cai, Christina Kendziorski, Susan L ThibeaultList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.2513590122Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1073/pnas.2513590122Direct OA link when available
- Concepts
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Stem cell, Cell biology, Biology, Progenitor cell, Homeostasis, Population, Regeneration (biology), Epithelium, Adult stem cell, Wnt signaling pathway, Epigenetics, Cell, Immunology, Larynx, Amniotic epithelial cells, Mucus, Progenitor, Cell type, Cellular differentiation, Transcriptome, Gene, Tight junction, Vocal folds, Regulation of gene expression, Gene expression, Cell culture, Notch signaling pathway, Respiratory epithelium, Side population, Somatic cell, PathologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
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34Number of works referenced by this work
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