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Series GSE25542 Query DataSets for GSE25542
Status Public on Nov 07, 2011
Title Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Cav1.2 that is associated with developmental delay and autism. We generated cortical neuronal precursor cells and neurons from induced pluripotent stem cells derived from individuals with Timothy syndrome. Cells from these individuals have defects in calcium (Ca2+) signaling and activity-dependent gene expression and show abnormalities in differentiation. Neurons from individuals with Timothy syndrome show increased expression of markers of the upper cortical layer and decreased expression of callosal projection markers. In addition, the mutation that causes Timothy syndrome leads to an increase in the production of neurons that synthesize norepinephrine and dopamine. This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase and atypical L-type–channel blocker. These findings provide strong evidence that Cav1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome.
Overall design Total RNA was isolated from control and TS cells: fibroblasts, iPSCs, neurospheres (at day 7 in suspension), neurons at rest (day 45 of differentiation) and neurons kept in 67mM KCl for 9h. For sample titles, D1,D2 and D3 represent independent differentiation experiments. The number after - represents the iPSC cell line number. GSE25542_non-normalized.txt.gz contains data for 5 outliers.
Contributor(s) Voineagu I
Citation(s) 22120178
Submission date Nov 22, 2010
Last update date Mar 20, 2017
Contact name Irina Voineagu
Organization name UCLA
Street address 695 Chrles E Young Dr
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL6883 Illumina HumanRef-8 v3.0 expression beadchip
Samples (59)
GSM627782 H9_D1_neurons
GSM627783 H9_D2_neurons
GSM627784 H9_D2_neurospheres
BioProject PRJNA134019

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
GSE25542_RAW.tar 3.9 Mb (http)(custom) TAR
GSE25542_non-normalized.txt.gz 18.8 Mb (ftp)(http) TXT
Raw data is available on Series record
Processed data included within Sample table

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