TY - JOUR
T1 - Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons
AU - Wang, Ping
AU - Zhao, Dejian
AU - Lachman, Herbert M.
AU - Zheng, Deyou
N1 - Funding Information:
This study is supported by NIH grants (MH099427 to HL and HL133120 to DZ). We thank the High Performance Computing division at the Albert Einstein College of Medicine for computing support. We also acknowledge supports by the Albert Einstein College of Medicine’s Rose F. Kennedy Intellectual and Developmental Disabilities Research Center and by the National Institutes of Health’s National Institute of Child Health and Human Development (NIH/ NICHD) grant P30 HD071593.
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41398-017-0058-6
DO - 10.1038/s41398-017-0058-6
M3 - Article
C2 - 29317598
AN - SCOPUS:85040507428
VL - 8
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 58
ER -