Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons

Brooke A. Derosa, Jimmy El Hokayem, Elena Artimovich, Catherine Garcia-Serje, Andre W. Phillips, Derek Van Booven, Jonathan E. Nestor, Lily Wang, Michael L. Cuccaro, Jeffery M. Vance, Margaret A. Pericak-Vance, Holly N. Cukier, Michael W. Nestor, Derek M. Dykxhoorn

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Potentially pathogenic alterations have been identified in individuals with autism spectrum disorders (ASDs) within a variety of key neurodevelopment genes. While this hints at a common ASD molecular etiology, gaps persist in our understanding of the neurodevelopmental mechanisms impacted by genetic variants enriched in ASD patients. Induced pluripotent stem cells (iPSCs) can model neurodevelopment in vitro, permitting the characterization of pathogenic mechanisms that manifest during corticogenesis. Taking this approach, we examined the transcriptional differences between iPSC-derived cortical neurons from patients with idiopathic ASD and unaffected controls over a 135-day course of neuronal differentiation. Our data show ASD-specific misregulation of genes involved in neuronal differentiation, axon guidance, cell migration, DNA and RNA metabolism, and neural region patterning. Furthermore, functional analysis revealed defects in neuronal migration and electrophysiological activity, providing compelling support for the transcriptome analysis data. This study reveals important and functionally validated insights into common processes altered in early neuronal development and corticogenesis and may contribute to ASD pathogenesis.

Original languageEnglish (US)
Article number8423
JournalScientific reports
Issue number1
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General


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