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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 16 NOV 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 12, pages 1915–1922, December 2011
How to Cite
Brennand, K. J. and Gage, F. H. (2011), Concise Review: The Promise of Human Induced Pluripotent Stem Cell-Based Studies of Schizophrenia. STEM CELLS, 29: 1915–1922. doi: 10.1002/stem.762
Author contributions: K.J.B. and F.H.G.: wrote the review together.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS October 18, 2011.
- Issue online: 16 NOV 2011
- Version of Record online: 16 NOV 2011
- Accepted manuscript online: 18 OCT 2011 03:31PM EST
- Manuscript Accepted: 25 SEP 2011
- Manuscript Received: 5 AUG 2011
- California Institute for Regenerative Medicine
- CIRM Grant. Grant Number: RL1-00649-1
- The Lookout and Mathers Foundation
- the Helmsley Foundation as well as Sanofi-Aventis
- Stem Cells;
Schizophrenia (SCZD) is a heritable developmental disorder. Although the molecular mechanism of disease remains unclear, insights into the disorder have been made through a vast array of experimental techniques. Together, magnetic resonance brain imaging, pharmacological, and post-mortem pathological studies have observed decreased brain volume, aberrant neurotransmitter signaling, reduced dendritic arborization, and impaired myelination in SCZD. Genome-wide association studies (GWAS) have identified common single nucleotide polymorphisms as well as rare copy number variants that contribute to SCZD, while mouse models of candidate SCZD genes show behavioral abnormalities and anatomical perturbations consistent with human disease. The advent of human induced pluripotent stem cells (hiPSCs) makes it possible to study SCZD using live human neurons with a genetic predisposition toward SCZD, even without knowledge of the genes interacting to produce the disease state. SCZD hiPSC neurons show cellular defects comparable to those identified in post-mortem human and mouse studies, and gene expression changes are consistent with predictions made by GWAS. SCZD hiPSC neurons represent a new tool to look beyond phenotype and begin to dissect the molecular mechanisms of SCZD. STEM CELLS 2011;29:1915–1922.