 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 08, 2014 |
| Title |
Smoking Dysregulates the Human Airway Basal Cell Transcriptome at COPD-linked Risk Locus 19q13.2 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Rationale: Genome-wide association studies (GWAS) and candidate gene studies have identified a number of loci linked to susceptibility of chronic obstructive pulmonary disease (COPD), a smoking-related disorder that originates in the airway epithelium.
Objectives: Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome linked, in part, to known GWAS/candidate gene loci.
Methods: Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n=10) and smokers (n=7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS and candidate gene studies to confer risk for COPD.
Measurements and Main Results: Smoker BC have 676 known genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10-4 compared to chance), including TGFB1, LTBP4, EGLN2 and NFKBIB, genes associated with risk for COPD.
Conclusions: These observations provide the first direct link of known genetic risks for smoking-related lung disease with the specific population of lung cells that undergoes the earliest changes associated with smoking.
|
| |
|
| Overall design |
The human airway basal cell transcriptome of 7 smokers versus 10 nonsmokers was compared using massive parallel RNA sequencing (Illumina HiSeq 2000).
|
| |
|
| Contributor(s) |
Ryan DM, Vincent TL, Salit J, Walters MS, Agosto-Perez F, Shaykhiev R, Strulovici-Barel Y, Hackett NR, Mezey JG, Crystal RG |
| Citation(s) |
24498427 |
| Submission date |
Jun 06, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Yael Strulovici-Barel |
| E-mail(s) |
yas2003@med.cornell.edu
|
| Organization name |
Weill Cornell Medical College
|
| Department |
Department of Genetic Medicine
|
| Lab |
Crystal
|
| Street address |
1300 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (17)
|
|
| Relations |
| BioProject |
PRJNA207365 |
| SRA |
SRP024274 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47718_RAW.tar |
11.6 Mb |
(http)(custom) |
TAR (of FPKM_TRACKING) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...