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| Status |
Public on Dec 08, 2016 |
| Title |
Single Cell RNA-Sequencing Identifies Diverse Roles of Epithelial Cells in Idiopathic Pulmonary Fibrosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease causing alveolar remodeling, inflammation, and fibrosis. We utilized single cell RNA-sequencing (scRNA-Seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of epithelial cells from normal human lung defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis. In contrast, scRNA-seq of IPF cells identified three distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and, an additional atypical "transitional" cell that contribute to pathological processes in IPF. Individual IPF cells frequently co-expressed alveolar AT1, AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development. Pathway analysis predicted aberrant activation of canonical signaling via TGF-ß, HIPPO/YAP, P53, and AKT-PI3 Kinase. Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells. Single cell transcriptomic analyses of respiratory epithelial cells identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF. Present scRNA-seq transcriptomic analysis of normal and IPF respiratory epithelial cells provides a rich data source to further explore lung health and disease.
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| Overall design |
Examination of expression profiling at single-cell level between IPF and Control.
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| Contributor(s) |
Xu Y, Mizuno T, Tang J, Funari VA, Stripp BR, Whitsett JA |
| Citation(s) |
27942595 |
| Submission date |
Sep 09, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jie Tang |
| E-mail(s) |
jie.tang@cshs.org
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| Organization name |
Cedars Sinai Medical Center
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| Street address |
8700 Beverly Blvd
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| City |
Los Angeles |
| ZIP/Postal code |
90048 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (540)
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| Relations |
| BioProject |
PRJNA342415 |
| SRA |
SRP087726 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86618_34816genes-540cells-tpm.txt.gz |
27.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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