Cellular reprogramming: a novel tool for investigating autism spectrum disorders

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in reciprocal social interaction and communication, as well as the manifestation of stereotyped behaviors. Despite much effort, ASDs are not yet fully understood. Advanced genetics and genomics technologies have recently identified novel ASD genes, and approaches using genetically engineered murine models or postmortem human brain have facilitated understanding ASD. Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) provides unprecedented opportunities in generating human disease models. Here, we present an overview of applying iPSCs in developing cellular models for understanding ASD. We also discuss future perspectives in the use of iPSCs as a source of cell therapy and as a screening platform for identifying small molecules with efficacy for alleviating ASD.

Figure 1. Overview of adopting induced pluripotent stem cell (iPSC) technology in autism spectrum disorder (ASD) study

ASD is a genetic neurodevelopmental disorder. Monogenic syndromic ASD is caused by well-defined genetic defect, including Rett syndrome, Fragile X syndrome, or Timothy syndrome. Advanced genomics tools are used to actively seek novel ASD genes. From skin biopsy or blood samples, patient-derived ASD-iPSCs can be generated. Cortical neurons that are most relevant neurons for ASD can be directed from iPSCs using well-established protocols (Table 1). The neuronal cells can be used to elucidate novel disease pathogenesis and to screen drugs as potential treatments. Recently developed gene editing technologies facilitate correcting the given mutation to provide isogenic control for in vitro diseases modeling or cell-based therapy.