Lin, Brian and Shah, Viral S. and Chernoff, Chaim and Sun, Jiawei and Shipkovenska, Gergana G. and Vinarsky, Vladimir and Waghray, Avinash and Xu, Jiajie and Leduc, Andrew D. and Hintschich, Constantin A. and Surve, Manalee Vishnu and Xu, Yanxin and Capen, Diane E. and Villoria, Jorge and Dou, Zhixun and Hariri, Lida P. and Rajagopal, Jayaraj (2024) Airway hillocks are injury-resistant reservoirs of unique plastic stem cells. NATURE, 629 (8013). ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)Abstract
Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer. In the lungs, recently identified epithelial structures known as hillocks can act as injury-resistant reservoirs of stem cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SQUAMOUS METAPLASIA; BASAL-CELLS; IN-VITRO; LUNG; ALVEOLAR; REGENERATION; EXPRESSION; NICHES; GENE; DIFFERENTIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Aug 2025 10:23 |
| Last Modified: | 20 Aug 2025 10:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65497 |
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