Comparative analysis of cellular expression pattern of schizophrenia risk genes in human versus mouse cortex

Zhang, Hai-Long1; Long, Jia-Wen1; Han, Wei1; Wang, Jiuzhou2; Song, Weichen3; Lin, Guan Ning4; Yin, Dong-Min1

2019-11-04

10.1186/s13578-019-0352-5

Cell and Bioscience   影响因子和分区

2045-3701

2045-3701

Background Schizophrenia is a common psychiatric disease with high hereditary. The identification of schizophrenia risk genes (SRG) has shed light on its pathophysiological mechanisms. Mouse genetic models have been widely used to study the function of SRG in the brain with a cell type specific fashion. However, whether the cellular expression pattern of SRG is conserved between human and mouse brain is not thoroughly studied. Results We analyzed the single-cell transcription of 180 SRG from human and mouse primary visual cortex (V1). We compared the percentage of glutamatergic, GABAergic and non-neuronal cells that express each SRG between mouse and human V1 cortex. Thirty percent (54/180) of SRG had significantly different expression rate in glutamatergic neurons between mouse and human V1 cortex. By contrast, only 5.6% (10/180) of SRG showed significantly different expression in GABAergic neurons, which is similar with the ratio of SRG (15/180) with species difference in total cell populations. Strikingly, the percentage of non-neuronal cells expressing all SRG are indistinguishable between human and mouse V1 cortex. We further analyzed the biological significance of differentially expressed SRG by gene ontology. The species-different SRG in glutamatergic neurons are highly expressed in dendrite and axon. They are enriched in the biological process of response to stimulus. However, the differentially expressed SRG in GABAergic neurons are enriched in the regulation of organelle organization. Conclusion GABAergic neurons are more conserved in the expression of SRG than glutamatergic neurons while the non-neuronal cells show the species conservation for the expression of all SRG. It should be cautious to use mouse models to study those SRG which show different cellular expression pattern between human and mouse cortex.

Schizophrenia Gene Single-cell RNA sequence Cortex Human and mouse Glutamatergic neuron GABAergic neuron Non-neuronal cell

SCI

英语

其他

Shanghai Key Laboratory of Psychotic Disorders Open Grant[13dz2260500]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000494709500001

BMC

Web of Science

1.East China Normal Univ, Sch Life Sci, Key Lab Brain Funct Genom, Minist Educ & Shanghai, Shanghai 200062, Peoples R China
2.Southern Univ Sci & Technol, Dept Math, Shenzhen, Peoples R China
3.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai, Peoples R China

Zhang, Hai-Long,Long, Jia-Wen,Han, Wei,et al. Comparative analysis of cellular expression pattern of schizophrenia risk genes in human versus mouse cortex[J]. Cell and Bioscience,2019,9(1).

Zhang, Hai-Long.,Long, Jia-Wen.,Han, Wei.,Wang, Jiuzhou.,Song, Weichen.,...&Yin, Dong-Min.(2019).Comparative analysis of cellular expression pattern of schizophrenia risk genes in human versus mouse cortex.Cell and Bioscience,9(1).

Zhang, Hai-Long,et al."Comparative analysis of cellular expression pattern of schizophrenia risk genes in human versus mouse cortex".Cell and Bioscience 9.1(2019).