Journal article
Transcriptomic responses of lung mesenchymal cells during pneumonia
JCI insight, Vol.10(7), e177084
04/08/2025
DOI: 10.1172/jci.insight.177084
PMCID: PMC11981624
PMID: 39998887
Abstract
The role of mesenchymal cells during respiratory infection is not well defined, including whether, which, and how the different types of mesenchymal cells respond. We collected all mesenchymal cells from lung single-cell suspensions of mice that were naïve (after receiving only saline vehicle), pneumonic (after intratracheal instillation of pneumococcus 24 hours previously), or resolved from infection (after non-lethal pneumococcal infections 6 weeks previously) and performed single-cell RNA sequencing. Cells clustered into five well-separated groups based on their transcriptomes: matrix fibroblasts, myofibroblasts, pericytes, smooth muscle cells, and mesothelial cells. Fibroblasts were the most abundant and could be further segregated into Pdgfra+Npnt+Ces1d+Col13a1+ alveolar fibroblasts and Cd9+Pi16+Sca1+Col14a1+ adventitial fibroblasts. The cells from naïve and resolved groups overlapped in dimension reduction plots, suggesting the mesenchymal cells returned to baseline transcriptomes after resolution. During pneumonia, all mesenchymal cells responded with altered transcriptomes, revealing a core response that had been conserved across cell types as well as distinct mesenchymal cell type-specific responses. The different subsets of fibroblasts induced similar gene sets, but the alveolar fibroblasts responded more strongly than the adventitial fibroblasts. These data demonstrated diverse and specialized immune activities of lung mesenchymal cells during pneumonia.
Details
- Title: Subtitle
- Transcriptomic responses of lung mesenchymal cells during pneumonia
- Creators
- Alicia M Soucy - Boston UniversityJourdan E Brune - University of WashingtonArchana Jayaraman - Boston UniversityAnukul T Shenoy - Boston UniversityFiliz T Korkmaz - Boston UniversityNeelou S Etesami - Boston UniversityBradley E Hiller - Boston UniversityIan Mc Martin - Boston UniversityWesley N Goltry - Boston UniversityCatherine T Ha - Boston UniversityNicholas A Crossland - Boston UniversityJoshua D Campbell - Boston UniversityThomas G Beach - Banner Sun Health Research InstituteKatrina E Traber - Boston UniversityMatthew R Jones - Boston UniversityLee J Quinton - Boston UniversityMarkus Bosmann - Boston UniversityCharles W Frevert - University of WashingtonJoseph P Mizgerd - Boston University
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.10(7), e177084
- DOI
- 10.1172/jci.insight.177084
- PMID
- 39998887
- PMCID
- PMC11981624
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Grant note
- NIH: R35-HL135756, R01-AI115053, R01-AI162850, R01-HL171499, R01-HL139641, R01-HL166588, T32-HL007035 NIH Shared Instrumentation Grants: S10-OD026983, S10-OD030269 NIH National Institute of Neurological Disorders and Stroke: U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders from the National Institute on Aging grants: P30 AG19610, P30 AG072980 Arizona Department of Health Services: 211002 Michael J. Fox Foundation for Parkinson's ResearchArizona Biomedical Research Commission: 4001, 0011, 05-901, 1001
We thank Anna Belkina and Brian Tilton of the Flow Cytometry Core for assistance with flow cytometry and FACS. We thank Hans P. Gertje and Aoife O'Connell of Boston University's National Emerging Infectious Diseases Laboratories for their histology expertise. We thank Caleb Weinreb of Harvard Medical School for expertise and help using the SPRING online platform. This work was funded by NIH grants R35-HL135756, R01-AI115053, R01-AI162850, and R01-HL171499 awarded to JPM; R01-HL139641 and R01-HL166588 awarded to MB; T32-HL007035 for support of trainees; as well as NIH Shared Instrumentation Grants S10-OD026983 and S10-OD030269. The Brain and Body Donation Program has been supported by the NIH National Institute of Neurological Disorders and Stroke grant U24 NS072026, National Brain and Tissue Resource for Parkinson's Disease and Related Disorders from the National Institute on Aging grants P30 AG19610 and P30 AG072980 at the Arizona Alzheimer's Disease Center, the Arizona Department of Health Services contract 211002 at the Arizona Alzheimer's Research Center, the Michael J. Fox Foundation for Parkinson's Research, and the Arizona Biomedical Research Commission contracts 4001, 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium.
- Language
- English
- Electronic publication date
- 02/25/2025
- Date published
- 04/08/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984795479102771
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