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Series GSE184384 Query DataSets for GSE184384
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
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.
 
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.
 
Contributor(s) Beppu AK, Stripp BR
Citation(s) 37726288
Submission date Sep 17, 2021
Last update date Sep 27, 2023
Contact name Barry Stripp
E-mail(s) barry.stripp@cshs.org
Phone 919-724-3069
Organization name Cedars Sinai Medical Center
Department Lung Institute
Lab AHSP 9401
Street address 8700 Beverly Blvd
City Los Angeles
State/province CA
ZIP/Postal code 90048
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (32)
GSM6439462 R1_epi_3dpi
GSM6439463 R1_epi_5dpi
GSM6439464 R1_epi_7dpi
Relations
BioProject PRJNA764926
SRA SRP338074

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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