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Series GSE132910 Query DataSets for GSE132910
Status Public on Jun 30, 2020
Title Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis (mouse scRNAseq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease associated with progressive scarring of lung tissue and declining pulmonary function in aging individuals. Here we employ data mining and single cell RNA sequencing (scRNAseq) to define candidate drivers of AT2 senescence in IPF lung tissue. We show that AT2 cells isolated from IPF lung tissue exhibit characteristic features of cellular senescence and reduced abundance of Sin3a, critical determinant of endodermal progenitor cell maintenance in the developing lung. Conditional loss of Sin3a within AT2 cells of the adult mouse lung activated a program of p53-dependent cellular senescence and AT2 cell depletion, leading to progressive pulmonary fibrosis. In contrast, ablation of AT2 cells through conditional activation of a DTA toxin gene led to transient fibrosis that resolved over time, suggesting that senescence of AT2 cells was a critical driver of progressive fibrosis. Activation of b6 integrin was observed within a subset of AT2 cells with Sin3a loss-of-function that localized to the advancing margin of advancing fibroproliferative lesions. Systemic inhibition of TGF signaling or delivery of senolytic drugs prevented lung fibrosis in Sin3a loss-of-function mice. Our findings establish a novel mouse model that recapitulates key pathological features of human IPA and show that p53-dependent senescence is a proximal regulator of TGF induction and progressive pulmonary fibrosis.
Overall design Single cell RNA-seq using 10x chromium system on enriched epithelial cells from 2 time points (4 week and 6 week after tamoxifen treated mouse lungs) of either control or Sin3a-LOF lungs, cells are isloated from 2 males and 2 females for each group of each time point.
Contributor(s) Yao C, Stripp BR
Citation(s) 32991815
Submission date Jun 18, 2019
Last update date Oct 01, 2020
Contact name Changfu Yao
Phone 424-315-4333
Organization name cedars-sinai medical center
Department Lung and Regenerative Medicine Institutes
Lab Stripp Lab
Street address 8700 Beverly Blvd. AHSP Room A9401
City los angeles
State/province Ca
ZIP/Postal code 90048
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM3896269 Epithelial cells, control_4wk
GSM3896270 Epithelial cells, control_6wk
GSM3896271 Epithelial cells, Sin3a-LOF_4wk
This SubSeries is part of SuperSeries:
GSE132915 Senescence rather than apoptosis of alveolar progenitor cells drives pulmonary fibrosis
BioProject PRJNA549452
SRA SRP201751

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Supplementary file Size Download File type/resource
GSE132910_RAW.tar 44.4 Mb (http)(custom) TAR (of H5)
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Raw data are available in SRA
Processed data provided as supplementary file

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