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Series GSE87281 Query DataSets for GSE87281
Status Public on Mar 21, 2017
Title SMN deficiency in spinal muscular atrophy causes widespread intron retention and DNA damage
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Spinal muscular atrophy is the leading genetic cause of infant mortality and is caused by homozygous loss of the SMN1 gene. We investigated global transcriptome changes in the spinal cord of inducible SMA mice. SMN depletion caused widespread retention of introns with weak splice sites or belonging to the minor (U12) class. We further demonstrated accumulation of DNA double strand breaks in the spinal cord of SMA mice and in human SMA cell culture models. DNA damage was partially rescued by suppressing the formation of R-loops, which accumulated over retained introns. We propose that instead of single gene effects, pervasive splicing defects caused by SMN deficiency trigger a global DNA damage and stress response, thus compromising motor neuron survival.
Overall design mRNA-seq: Total spinal cord from SMA and Control mice (rescue experiment) at d20 and d30; human SH-SY5Y cells expressing SMN or Control shRNA for 7d; human iPSC-derived motor neurons expressing SMN or Control shRNA for 5d; total spinal cord from SMA and Control mice (induction experiment) at d10, d20, and d30.
DRIP-seq: SH-SY5Y cells expressing SMN or Control shRNA for 7d and immunoprecipitated with S9.6 antibody targeting RNA:DNA hybrids.
Contributor(s) Jangi M, Carulli JP
Citation(s) 28270613
Submission date Sep 22, 2016
Last update date May 15, 2019
Contact name John Carulli
Organization name Biogen
Department Computational Biology and Genomics
Lab Translational Genomics
Street address 115 Broadway
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (101)
GSM2326771 mRNA PBS d20 rep1
GSM2326772 mRNA PBS d20 rep2
GSM2326773 mRNA PBS d20 rep3
BioProject PRJNA343962
SRA SRP090328

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE87281_SHSY5Y.RSEM.genes.results.human_names.txt.gz 1.0 Mb (ftp)(http) TXT
GSE87281_SHSY5Y_shSMN-1_vs_shCtrl_FDR0.05.sepnames.txt.gz 934.7 Kb (ftp)(http) TXT
GSE87281_SHSY5Y_shSMN-2_vs_shCtrl_FDR0.05.sepnames.txt.gz 1.2 Mb (ftp)(http) TXT 2.2 Mb (ftp)(http) TXT
GSE87281_SMAinduction_SKIPvsCTRL_alltimepoints_DESeq2ContrastTest_splitnames.txt.gz 8.6 Mb (ftp)(http) TXT
GSE87281_SMArescueIJKvsE.DESeq2ContrastTest.txt.gz 3.7 Mb (ftp)(http) TXT
GSE87281_SMArescue_all_RSEM.genes.results.human_names_split.txt.gz 2.6 Mb (ftp)(http) TXT
GSE87281_SMArescue_d20d30_DvsE_all_DESeqOutput.txt.gz 2.7 Mb (ftp)(http) TXT
GSE87281_hiPSC-MN.RSEM.genes.results.human_names.txt.gz 931.3 Kb (ftp)(http) TXT
GSE87281_hiPSC_shSMN-1_vs_shCtrl_FDR0.05.sepnames.txt.gz 145.1 Kb (ftp)(http) TXT
GSE87281_hiPSC_shSMN-2_vs_shCtrl_FDR0.05.sepnames.txt.gz 426.0 Kb (ftp)(http) TXT
GSE87281_shCtrlrep1_S96_vs_IgG_summits_win250rep2.bed.gz 165.6 Kb (ftp)(http) BED
GSE87281_shSMNrep1_S96_vs_IgG_summits_win250rep2.bed.gz 243.2 Kb (ftp)(http) BED
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Processed data are available on Series record

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