Modeling Rett syndrome with stem cells

Abstract

The discovery that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) raised the exciting possibility of modeling diseases with patient-specific cells. Marchetto et al. (2010) now use iPSC technology to generate, characterize, and treat an in vitro model for the autism spectrum disorder Rett syndrome.

Figure 1. Using iPSCs to model Rett syndrome in vitro

Mutations in the methyl-CpG binding protein (MeCP2) gene cause the neurodevelopmental disorder Rett syndrome. Marchetto et al. (2010) isolate fibroblasts from Rett patients with MeCP2 mutations. They then reprogram these cells into induced pluripotent stem cells (iPSCs) by the exogenous expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc. These Rett-iPSCs can then differentiate into neurons in vitro, recapitulating several of the defects found in Rett syndrome patients and in animal models of the disease. These defects can be partially reversed by candidate drugs, suggesting that this disease model will facilitate large-scale drug screens and future mechanistic studies of Rett syndrome.