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Series GSE264128 Query DataSets for GSE264128
Status Public on Jul 24, 2024
Title Spatial analysis of murine lungs exposed to fibrogenic stress
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Other
Summary Acute inflammatory exacerbations (AIEs) represent immune-driven deteriorations of many chronic lung conditions, including COPD, asthma, and pulmonary fibrosis (PF). The first line of therapy is represented by broad-spectrum immunomodulation. To better study immune cell heterogeneity during AIE-PF, this work leverages a clinically relevant model of inflammatory exacerbations triggered by mutation in the alveolar epithelial type 2 cell Surfactant Protein-C gene [SP-CI73T]. SP-CI73T mice received corn oil (controls) or tamoxifen (175 mg/kg, orally) to excise a neomycin cassette placed on the surfacant protein C gene locus, hence inducing the expression of the mutant transcript. We have previously shown that a complex inflammatory response arises by 14 days post tamoxifen administration. Paraffin sections of murine lungs were therefore collected in controls and 14 days post induction. Immunofluorescence for DNA, CD45, CD68 was performed to identify macrophages (CD45+CD68+) and non-immune ("other", DNA+CD45-) cells within healthy, peri-injured and injured regions of the lung. A total of 12 regions (680um x 700um in size) were selected and macrophages and "other" cells isolated. RNA sequencing was then performed. Principal component and pathway analysis revealed spatial heterogeneity with an hyperactive peri-injured compartment (extracellular matrix remodeling, innate and adaptive immunity, senescence). Cells isolated from injured areas of the lung were relatively quiescent. These results illustrate regional heterogeneity in immune and non-immune cells of the lung during fibrogenic stress.
 
Overall design Paraffin-embedded sections of SP-C mutant lungs (one oil treated control and one 14 day injured) were assessed through spatial analysis of CD45+CD68+ macrophages and DNA+CD45- non-immune ("other") cells.
 
Contributor(s) Venosa A, Noll J
Citation(s) 39100672
Submission date Apr 16, 2024
Last update date Aug 29, 2024
Contact name Alessandro Venosa
E-mail(s) Alessandro.venosa@pharm.utah.edu
Organization name University of Utah
Department Pharmacology and Toxicology
Street address 30 2000 E, Rm. 3952
City Salt Lake City
State/province UT
ZIP/Postal code 84112
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (25)
GSM8212499 no template control
GSM8212500 healthy region 1_SP-C mutant lung tissue (immune)
GSM8212501 healthy region 1_SP-C mutant lung tissue (non immune)
Relations
BioProject PRJNA1101031

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
GSE264128_Fluorescence_high_res_image_111_CTL_top_-_113_14d_injured_bottom_.jpg.gz 338.3 Mb (ftp)(http) JPG
GSE264128_Mm_R_NGS_WTA_v1.0.pkc.gz 1.8 Mb (ftp)(http) PKC
GSE264128_RAW.tar 1.3 Mb (http)(custom) TAR (of DCC)
GSE264128_Venosa_-_LabWorksheet_Spatial_transcriptomics.txt.gz 762 b (ftp)(http) TXT
GSE264128_Venosa_fibrosis_111_and_113_dcc-metadata.csv.gz 4.7 Kb (ftp)(http) CSV
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