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Series GSE52202 Query DataSets for GSE52202
Status Public on Nov 07, 2013
Title iPSC derived motor neuron cultures from C9ORF72 carriers
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. We report a cellular model of C9-ALS with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. Transcription of the repeat was increased, leading to accumulation of GGGGCC repeat–containing RNA foci selectively in C9-ALS iPSC-derived motor neurons. Repeat-containing RNA foci colocalized with hnRNPA1 and Pur-α, suggesting that they may be able to alter RNA metabolism. C9-ALS motor neurons showed altered expression of genes involved in membrane excitability including DPP6, and demonstrated a diminished capacity to fire continuous spikes upon depolarization compared to control motor neurons. Antisense oligonucleotides targeting the C9ORF72 transcript suppressed RNA foci formation and reversed gene expression alterations in C9-ALS motor neurons. These data show that patient-derived motor neurons can be used to delineate pathogenic events in ALS.
 
Overall design Transcriptome profiling from iPSC derived motor neurons compared to controls
 
Contributor(s) Baloh RH
Citation(s) 24154603
Submission date Nov 07, 2013
Last update date Mar 20, 2019
Contact name Robert Baloh
E-mail robert.baloh@csmc.edu
Organization name Cedars-Sinai Medical Center
Street address 8700 Beverly Blvd
City Los Angeles
State/province CA
ZIP/Postal code 90048
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (8)
GSM1261105 Control 00i
GSM1261106 Control 03i
GSM1261107 Control 14i
Relations
BioProject PRJNA227155
SRA SRP032798

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
GSE52202_iPSCMN_RPKM_RS10162012.txt.gz 654.2 Kb (ftp)(http) TXT
Raw data are available in SRA
Processed data is available on Series record

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