Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages.
Irene G WongJillian StarkVanNashlee YaAaron L MoyeAlan Baez VazquezSusanna M DangAndrea ShehajMaral J RouhaniRoderick BronsonSam M JanesSamuel P RowbothamMargherita PaschiniRuth A FranklinCarla F KimPublished in: bioRxiv : the preprint server for biology (2024)
Acute injury in the airways or the lung activates local progenitors and stimulates changes in cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted. We utilized mouse models of airway-specific epithelial injury to examine secondary tissue-wide alveolar, immune, and mesenchymal responses. Single-cell transcriptomics and in vivo validation revealed transient, tissue-wide proliferation of alveolar type 2 (AT2) progenitor cells after club cell-specific ablation. The AT2 cell proliferative response was reliant on alveolar macrophages (AMs) via upregulation of Spp1 which encodes the secreted factor Osteopontin. A previously uncharacterized mesenchymal population we termed Mesenchymal Airway/Adventitial Niche Cell 2 (MANC2) also exhibited dynamic changes in abundance and a pro-fibrotic transcriptional signature after club cell ablation in an AM-dependent manner. Overall, these results demonstrate that acute airway damage can trigger distal lung responses including altered cell-cell interactions that may contribute to potential vulnerabilities for further dysregulation and disease.
Keyphrases
- single cell
- rna seq
- cell therapy
- stem cells
- gene expression
- high throughput
- intensive care unit
- mouse model
- cystic fibrosis
- signaling pathway
- liver failure
- mesenchymal stem cells
- transcription factor
- brain injury
- minimally invasive
- risk assessment
- blood brain barrier
- respiratory failure
- heat shock
- acute respiratory distress syndrome
- microbial community
- radiofrequency ablation
- genetic diversity
- clinical evaluation