Transcriptomics

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Transcriptomic Comparison of Neuronal Development Stages using Induced Pluripotent Stem Cells from Bipolar Disorder Patients


ABSTRACT: Fibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L). Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold). Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways GSK3β signaling may play an important role in the pathophysiology of BPD. Samples for each of four iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L) were analyzed

ORGANISM(S): Homo sapiens  

SUBMITTER: Rosamund C Smith   Steven M Paul  Jeffrey L Dage  Kwi H Kim  Rachelle J Sells Galvin  Kalpana M Merchant  Janice A Egeland  Jiangang Liu 

PROVIDER: E-GEOD-74358 | ArrayExpress | 2015-10-26

SECONDARY ACCESSION(S): GSE74358PRJNA299812

REPOSITORIES: GEO, ArrayExpress

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Publications

Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree.

Kim Kwi Hye KH   Liu Jiangang J   Sells Galvin Rachelle J RJ   Dage Jeffrey L JL   Egeland Janice A JA   Smith Rosamund C RC   Merchant Kalpana M KM   Paul Steven M SM  

PloS one 20151110 11


Fibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (terme  ...[more]

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