Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons

Ping Wang, Dejian Zhao, Herbert M. Lachman, Deyou Zheng

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) is highly heritable but genetically heterogeneous. The affected neural circuits and cell types remain unclear and may vary at different developmental stages. By analyzing multiple sets of human single cell transcriptome profiles, we found that ASD candidates showed relatively enriched gene expression in neurons, especially in inhibitory neurons. ASD candidates were also more likely to be the hubs of the co-expression gene module that is highly expressed in inhibitory neurons, a feature not detected for excitatory neurons. In addition, we found that upregulated genes in multiple ASD cortex samples were enriched with genes highly expressed in inhibitory neurons, suggesting a potential increase of inhibitory neurons and an imbalance in the ratio between excitatory and inhibitory neurons in ASD brains. Furthermore, the downstream targets of several ASD candidates, such as CHD8, EHMT1 and SATB2, also displayed enriched expression in inhibitory neurons. Taken together, our analyses of single cell transcriptomic data suggest that inhibitory neurons may be a major neuron subtype affected by the disruption of ASD gene networks, providing single cell functional evidence to support the excitatory/inhibitory (E/I) imbalance hypothesis.

Original languageEnglish (US)
Article number58
JournalTranslational Psychiatry
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Gene Expression
Neurons
Gene Regulatory Networks
Autism Spectrum Disorder
Single-Cell Analysis
Transcriptome
Genes
Brain

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons. / Wang, Ping; Zhao, Dejian; Lachman, Herbert M.; Zheng, Deyou.

In: Translational Psychiatry, Vol. 8, No. 1, 58, 01.12.2018.

Research output: Contribution to journalArticle

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