Differential expression analysis of schizophrenia susceptibility genes in single cells of human and mouse brain / 上海交通大学学报（医学版）

ABSTRACT

Objective: To investigate the expression patterns of schizophrenia susceptibility genes in different neuronal cell types of human and mouse brains. Methods: Schizophrenia susceptibility genes were studied based on four genetic study methods, including genome-wide association study, linkage and association study, copy number variation study and convergent functional genomics study. Single cell RNA-seq data of human and mouse brains were used to explore the expression patterns of schizophrenia susceptibility genes in specific cell types of neurons, astrocytes, microglia, oligodendrocytes, oligodendrocyte progenitor cells. Furthermore, the functions of schizophrenia risk genes identified only in human brains were analyzed by functional annotation tools from the DAVID database. Results: Comparisons were made about single cell RNA-seq data between human and mouse brains, and there existed distinct expression patterns of schizophrenia susceptibility genes across species. Neurons, astrocytes and oligodendrocytes from both human and mouse were shown to have more co-expressed schizophrenia susceptibility genes, while co-expression of schizophrenia susceptibility genes in microglia and oligodendrocyte progenitor cells rarely existed. In addition, schizophrenia risk genes expressed only in human were involved in the regulation of neural synaptic plasticity and calcium signaling pathway. Conclusion: The schizophrenia susceptibility genes have distinct expression profiles at the single cell level in human and mouse brains, which provides clues and evidence for revealing the etiological mechanism of schizophrenia based on mouse model research.