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Series GSE63756 Query DataSets for GSE63756
Status Public on Dec 02, 2014
Title The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding how the ER stress response impacts human disease is to determine how the transcriptional response to ER stress varies among individuals. The genetic diversity of the eight mouse Collaborative Cross (CC) founder strains allowed us to determine how genetic variation impacts the ER stress transcriptional response. We used tunicamycin, a drug commonly used to induce ER stress, to elicit an ER stress response in mouse embryonic fibroblasts (MEFs) derived from the CC founder strains and measured their transcriptional responses. We identified hundreds of genes that differed in response to ER stress across these genetically diverse strains. Strikingly, inflammatory response genes differed most between strains; major canonical ER stress response genes showed relatively invariant responses across strains. To uncover the genetic architecture underlying these strain differences in ER stress response, we measured the transcriptional response to ER stress in MEFs derived from a subset of F1 crosses between the CC founder strains. We found a unique layer of regulatory variation that is only detectable under ER stress conditions. Over 80% of the regulatory variation under ER stress derives from cis-regulatory differences. This is the first study to characterize the genetic variation in ER stress transcriptional response in the laboratory mouse. Our findings indicate that the ER stress transcriptional response is highly variable among strains and arises from genetic variation in individual downstream response genes, rather than major signaling transcription factors. These results have important implications for understanding how genetic variation impacts the ER stress response, an important component of many human diseases.
Overall design We investigated the genetic variation in ER stress transcriptional response in mouse embryonic fibroblasts (MEFs) across eight mouse strains: A/J, C57BL/6J, 129S1Sv/ImJ, NOD/ShiLtJ, NZO/H1LtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. MEFs from each strain were treated with a control DMSO or ER stress-inducing drug, Tunicamycin (TM). To identify the genetic architecture underlying this genetic variation, MEFs from F1 strains were also studied. MEFs from the following F1s were evaluated: C57BL/6J X CAST/EiJ, C57BL/6J X 129S1Sv/ImJ, C57BL/6J X NOD/ShiLtJ, C57BL/6J X NZO/H1LtJ, and C57BL/6J X WSB/EiJ. Again F1 MEFS were treated with either DMSO or TM. There are two or three replicates for each sample.
Contributor(s) Chow CY, Clark AG
Citation(s) 25651210
Submission date Dec 01, 2014
Last update date May 15, 2019
Contact name Clement Y Chow
Phone 6072551707
Organization name Cornell University
Street address 227 Biotech Bldg
City Ithaca
State/province NY
ZIP/Postal code 14853-2703
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (68)
GSM1556707 129 control replicate2
GSM1556708 129 control replicate3
GSM1556709 129 Tunicamycin replicate1
BioProject PRJNA268980
SRA SRP050399

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Supplementary file Size Download File type/resource
GSE63756_129S1SvImJ_control_TM_FPKM.csv.gz 350.3 Kb (ftp)(http) CSV
GSE63756_AJ_control_TM_FPKM.csv.gz 416.3 Kb (ftp)(http) CSV
GSE63756_C57BL6J_control_TM_FPKM.csv.gz 289.9 Kb (ftp)(http) CSV
GSE63756_CASTEiJ_control_TM_FPKM.csv.gz 289.2 Kb (ftp)(http) CSV
GSE63756_F1_C57BL6Jx129S1SvImJ_control_TM_FPKM.csv.gz 409.3 Kb (ftp)(http) CSV
GSE63756_F1_C57BL6JxCASTEiJ_control_TM_FPKM.csv.gz 344.6 Kb (ftp)(http) CSV
GSE63756_F1_C57BL6JxNODShiLtJ_control_TM_FPKM.csv.gz 350.9 Kb (ftp)(http) CSV
GSE63756_F1_C57BL6JxNZOH1LtJ_control_TM_FPKM.csv.gz 418.5 Kb (ftp)(http) CSV
GSE63756_F1_C57BL6JxWSBEiJ_control_TM_FPKM.csv.gz 394.4 Kb (ftp)(http) CSV
GSE63756_NODShiLtJ_control_TM_FPKM.csv.gz 353.5 Kb (ftp)(http) CSV
GSE63756_NZOH1LtJ_control_TM_FPKM.csv.gz 350.6 Kb (ftp)(http) CSV
GSE63756_PWKPhJ_control_TM_FPKM.csv.gz 421.4 Kb (ftp)(http) CSV
GSE63756_WSBEiJ_control_TM_FPKM.csv.gz 324.1 Kb (ftp)(http) CSV
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