Transcriptomic analysis of induced pluripotent stem cells derived from patients with bipolar disorder from an old order amish pedigree

Kwi Hye Kim, Jiangang Liu, Rachelle J Sells Galvin, Jeffrey L. Dage, Janice Egeland, Rosamund C. Smith, Kalpana M. Merchant, Steven M. Paul

Research output: Contribution to journalArticle

14 Scopus citations

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 may play an important role in the pathophysiology of BPD.

Original languageEnglish (US)
Article number0142693
JournalPLoS One
Volume10
Issue number11
DOIs
StatePublished - Nov 10 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Kim, K. H., Liu, J., Galvin, R. J. S., Dage, J. L., Egeland, J., Smith, R. C., Merchant, K. M., & Paul, S. M. (2015). Transcriptomic analysis of induced pluripotent stem cells derived from patients with bipolar disorder from an old order amish pedigree. PLoS One, 10(11), [0142693]. https://doi.org/10.1371/journal.pone.0142693