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Status |
Public on Aug 08, 2023 |
Title |
Epithelial Plasticity and Innate Immune Activation Promote Lung Tissue Remodeling following Respiratory Viral Infection. |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
As observed in mice with genetic depletion of stem cells, epithelial plasticity is a critical component of tissue repair in response to injury; however, the physiological relevance of this process and the involved progenitor populations are not well understood. Severe respiratory viral infection and chronic lung disease share pathological features including stem cell loss in the gas-exchange regions, basal cell (BC) hyperplasia in small airways, and innate immune activation. Collectively, these processes contribute to epithelial remodeling and loss of diffusion capacity. Here, we show that small airways harbor a previously undescribed lineage of secretory cells, intralobar serous (IS) cells, that are activated to assume BC fates following influenza virus infection. Nascent BC were distinguished from pre-existing BC by high expression of IL-22Ra1 and a dependency on innate immune activation and local IL-22 production for self-renewal and colonization of injured alveoli. Resolution of virus-elicited inflammation and the associated decline in IL-22 signaling resulted in basal to serous re-differentiation in repopulated alveoli, and increased local expression of antimicrobial factors, but failed to replace normal alveolar epithelium. We define a mechanism whereby epithelial plasticity confers protection against mortality from acute respiratory viral infection but has potential to contribute to progressive lung remodeling and life-threatening declines in lung function among patients with chronic lung disease.
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Overall design |
Single cell RNAseq was used to assess dynamic changes in gene expression and cell representation at indicated time points following influenza induced acute lung injury (naïve, 3, 5 , 7, 9 , 11, 14, 17, 21, 120, 240). Immune and Epithelial cell were enriched prior to cell capture by FACS.
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Contributor(s) |
Beppu AK, Stripp BR |
Citation(s) |
37726288 |
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Submission date |
Sep 17, 2021 |
Last update date |
Sep 27, 2023 |
Contact name |
Barry Stripp |
E-mail(s) |
barry.stripp@cshs.org
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Phone |
919-724-3069
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Organization name |
Cedars Sinai Medical Center
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Department |
Lung Institute
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Lab |
AHSP 9401
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Street address |
8700 Beverly Blvd
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City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90048 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (32)
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Relations |
BioProject |
PRJNA764926 |
SRA |
SRP338074 |
Supplementary file |
Size |
Download |
File type/resource |
GSE184384_HTO_info.xlsx |
9.0 Kb |
(ftp)(http) |
XLSX |
GSE184384_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of CSV, JPG, JSON, MTX, PNG, RDS, TIFF, TSV) |
GSE184384_influenza_timecourse_epithelial.rds.gz |
870.3 Mb |
(ftp)(http) |
RDS |
GSE184384_influenza_timecourse_immune.rds.gz |
404.9 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
Processed data provided as supplementary file |
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