Contribution of Trp63CreERT2-labeled cells to alveolar regeneration is independent of tuft cells
Abstract
Viral infection often causes severe damage to the lungs, leading to the appearance of ectopic basal cells (EBCs) and tuft cells in the lung parenchyma. Thus far, the roles of these ectopic epithelial cells in alveolar regeneration remain controversial. Here, we confirm that the ectopic tuft cells are originated from EBCs in mouse models and COVID-19 lungs. The differentiation of tuft cells from EBCs is promoted by Wnt inhibition while suppressed by Notch inhibition. Although progenitor functions have been suggested in other organs, pulmonary tuft cells don’t proliferate or give rise to other cell lineages. Consistent with previous reports, Trp63CreERT2 and KRT5-CreERT2-labeled ectopic EBCs do not exhibit alveolar regeneration potential. Intriguingly, when tamoxifen was administrated post-viral infection, Trp63CreERT2 but not KRT5-CreERT2 labels islands of alveolar epithelial cells that are negative for EBC biomarkers. Furthermore, germline deletion of Trpm5 significantly increases the contribution of Trp63CreERT2-labeled cells to the alveolar epithelium. Although Trpm5 is known to regulate tuft cell development, complete ablation of tuft cell production fails to improve alveolar regeneration in Pou2f3-/- mice, implying that Trpm5 promotes alveolar epithelial regeneration through a mechanism independent of tuft cells.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 21, 2022
- Source ID
- 10.7554/elife.78217
Entities
People
- Anjali Saqi
- Benjamin Izar
- Charles W. Emala
- Hongmei Mou
- Huachao Huang
- Ichiro Matsumoto
- Jana Biermann
- Jennifer A. Danielsson
- Jia Liu
- Jian Zhu
- Jianwen Que
- Jie Sun
- Johannes C. Melms
- Li Qiang
- Manli Wang
- Ming Jiang
- Timothy C Wang
- Wellington V Cardoso
- Yihan Zhang
- Ying Yang
- Yinshan Fang
- Yiwu Zhou
- Zhihong Hu
Organizations
- Children's Hospital of Zhejiang University
- Columbia University
- Columbia University Irving Medical Center
- Cystic Fibrosis Foundation
- Harvard Stem Cell Institute
- Health Resources in Action
- Huazhong University of Science and Technology
- Massachusetts General Hospital
- Monell Chemical Senses Center
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- Ohio State University
- Stanford University
- State Key Laboratory of Virology
- United States Department of Defense
- University of Virginia