Transcriptomic responses of lung mesenchymal cells during pneumonia

• DOI: 10.1172/jci.insight.177084
• Publication Date: 2025-02-25T17:00:14Z
• Authors: Alicia M. Soucy; Jourdan E. Brune; Archana Jayaraman; Anukul T. Shenoy; Filiz T. Korkmaz; Neelou S. Etesami; Bradley E. Hiller; Ian M.C. Martin; Wesley N. Goltry; Catherine T. Ha; Nicholas A. Cross...; Joshua D. Campbell; Thomas G. Beach; Katrina E. Traber; Matthew R. Jones; Lee J. Quinton; Markus Bosmann; Charles W. Frevert; Joseph P. Mizgerd
• Keywords: PDGFRA; Mesenchyme; Myofibroblast; Cell type

The role of mesenchymal cells during respiratory infection is not well defined, including whether, which, and how the different types respond. We collected all from lung single-cell suspensions mice that were naïve (after receiving only saline vehicle), pneumonic intratracheal instillation pneumococcus 24 hours previously), or resolved non-lethal pneumococcal infections 6 weeks previously) performed RNA sequencing. Cells clustered into five well-separated groups based on their transcriptomes: matrix fibroblasts, myofibroblasts, pericytes, smooth muscle cells, mesothelial cells. Fibroblasts most abundant could be further segregated Pdgfra+Npnt+Ces1d+Col13a1+ alveolar fibroblasts Cd9+Pi16+Sca1+Col14a1+ adventitial fibroblasts. overlapped in dimension reduction plots, suggesting returned to baseline transcriptomes after resolution. During pneumonia, responded with altered transcriptomes, revealing a core response had been conserved across cell as distinct type-specific responses. subsets induced similar gene sets, but more strongly than These data demonstrated diverse specialized immune activities pneumonia.