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Transl Psychiatry. 2018 Jan 10;8(1):13. doi: 10.1038/s41398-017-0058-6.

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

Wang P1, Zhao D1, Lachman HM1,2,3,4, Zheng D5,6,7.

Author information

1
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA.
2
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA.
3
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA.
4
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA.
5
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA. deyou.zheng@einstein.yu.edu.
6
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA. deyou.zheng@einstein.yu.edu.
7
Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, USA. deyou.zheng@einstein.yu.edu.

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.

PMID:
29317598
PMCID:
PMC5802446
DOI:
10.1038/s41398-017-0058-6
[Indexed for MEDLINE]
Free PMC Article

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