Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells

Erika Pedrosa, Vladislav Sandler, Abhishek Shah, Reed Carroll, Chanjung Chang, Shira Rockowitz, Xingyi Guo, Deyou Zheng, Herbert M. Lachman

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Induced pluripotent stem cell (iPSC) technology has the potential to transform regenerative medicine. It also offers a powerful tool for establishing in vitro models of disease, in particular, for neuropsychiatric disorders where live human neurons are essentially impossible to procure. Using iPSCs derived from three schizophrenia (SZ) patients, one of whom has 22q11.2del (velocardiofacial syndrome; VCFS), the authors developed a culture system to study SZ on a molecular and cellular level. SZ iPSCs were differentiated into functional, primarily glutamatergic neurons that were able to fire action potentials after ∼8 weeks in culture. Early differentiating neurons expressed a number of transcription factors/chromatin remodeling proteins and synaptic proteins relevant to SZ pathogenesis, including ZNF804A, RELN, CNTNAP2, CTNNA2, SMARCA2, and NRXN1. Although a small number of lines were developed in this preliminary study, the SZ line containing 22q11.2del showed a significant delay in the reduction of endogenous OCT4 and NANOG expression that normally occurs during differentiation. Constitutive expression of OCT4 has been observed in Dgcr8-deficient mouse embryonic stem cells (mESCs); DGCR8 maps to the 22q11.2-deleted region. These findings demonstrate that the method of inducing neural differentiation employed is useful for disease modeling in SZ and that the transition of iPSCs with 22q11.2 deletions towards a differentiated state may be marked by subtle changes in expression of pluripotency-associated genes.

Original languageEnglish (US)
Pages (from-to)88-103
Number of pages16
JournalJournal of Neurogenetics
Volume25
Issue number3
DOIs
StatePublished - Oct 1 2011

Keywords

  • Autism
  • Bipolar disorder
  • Ipsc
  • Neurogenesis
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells'. Together they form a unique fingerprint.

Cite this