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Series GSE87495 Query DataSets for GSE87495
Status Public on Dec 31, 2016
Title DUX4-induced dsRNA and MYC mRNA Stabilization Activate Apoptotic Pathways in Human Cell Models of Facioscapulohumeral Dystrophy
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Facioscapulohumeral muscular dystophy (FSHD) is caused by the mis-expression of DUX4 in skeletal muscle cells. DUX4 is a transcription factor that activates genes normally associated with stem cell biology and its mis-expression in FSHD cells results in apoptosis. To identify genes and pathways necessary for DUX4-mediated apoptosis, we performed an siRNA screen in an RD rhabdomyosarcoma cell line with an inducible DUX4 transgene. Our screen identified components of the MYC-mediated apoptotic pathway and the double-stranded RNA (dsRNA) innate immune response pathway as mediators of DUX4-induced apoptosis. Further investigation revealed that DUX4 expression led to increased MYC mRNA, accumulation of nuclear dsRNA foci, and activation of the dsRNA response pathway in both RD cells and human myoblasts. Nuclear dsRNA foci were associated with aggregation of the exon junction complex component EIF4A3. The elevation of MYC mRNA, dsRNA accumulation, and EIF4A3 nuclear aggregates in FSHD muscle cells suggest that these processes might contribute to FSHD pathophysiology.
Overall design RNA-seq of human rhabdomyosarcoma cells with an inducible DUX4 transgene (RD-DUX4i) cells was performed on RNA samples collected from 3 separate experimental replicates induced from 16-18 hours with doxycycline, as indicated and compared to the respective uninduced condition.
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Contributor(s) Shadle SC, Zhong JW, Campbell AE, Conerly ML, Jagannathan S, Wong C, Morello TD, Tapscott SJ
Citation(s) 28273136
Submission date Sep 29, 2016
Last update date May 15, 2019
Contact name Stephen Tapscott
Organization name Fred Hutch Cancer Research Center
Department Human Biology
Lab Tapscott
Street address 1100 Fairview N. Ave
City Seattle
State/province WASHINGTON
ZIP/Postal code 98103
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM2332607 Sample_1-RD-dux4_no-dox_16hr_expt11
GSM2332608 Sample_2-RD-dux4_with-dox_16hr_expt11
GSM2332609 Sample_3-RD-dux4_no-dox_16hr_expt14
BioProject PRJNA344913
SRA SRP090635

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Supplementary file Size Download File type/resource
GSE87495_dds.rda.gz 8.7 Mb (ftp)(http) RDA
GSE87495_results_dds_gencode22.csv.gz 1.5 Mb (ftp)(http) CSV
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