上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2019, Vol. 39 ›› Issue (2): 113-.doi: 10.3969/j.issn.1674-8115.2019.02.002

• 论著·基础研究 • 上一篇    下一篇

精神分裂症易感基因在人类与小鼠脑组织单细胞中的表达差异分析

程影 1，鞠培俊 1，王卫娣 1，方钰 1，林关宁 1, 2，崔东红 1   

  1. 1.上海交通大学医学院附属第九人民医院 ·口腔医学院牙周病科，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011；2.中国人民解放军 93313部队，长春 130111；3.中国人民解放军第 208医院 461临床部，长春 130021
  • 出版日期:2019-02-28 发布日期:2019-03-19
  • 通讯作者: 崔东红，电子信箱：manyucc@126.com。
  • 作者简介:程影（1992—），女，硕士生；电子信箱： sjmedical_cy@163.com。
  • 基金资助:
    国家重点研发计划精准医学研究重点专项 (2017YFC0909200)；国家自然科学基金 (81671336)；上海市科学技术委员会科研计划项目 (13dz2260500)

Differential analysis of schizophrenia susceptibility genes in single cells of human and mobrain

CHENG Ying1, JU Pei-jun1, WANG Wei-di1, FANG Yu1, LIN Guan-ning1, 2, CUI Dong-hong1   

  1. 1. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; 2. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
  • Online:2019-02-28 Published:2019-03-19
  • Supported by:
    National Key Research and Development Plan, 2017YFC0909200; National Natural Science Foundation of China, 81671336; Shanghai Committee of Science and Technology Research Project, 13dz2260500

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摘要： 目的 ·探究精神分裂症易感基因在人类和小鼠脑组织各类细胞中的表达模式。方法 ·采用 4类遗传研究方法（全基因组关联研究、连锁和关联研究、拷贝数变异研究和多模态功能基因组学研究）发现精神分裂症易感基因。利用人类和小鼠脑组织单细胞 RNA测序 (RNA-seq)数据，分析精神分裂症易感基因在神经元、星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质前体细胞的表达模式，并采用 DAVID数据库对人类脑组织单细胞特异表达的易感基因进行功能富集分析。结果 ·精神分裂症易感基因在人类和小鼠脑组织单细胞的表达模式存在差异。其中，在人类和小鼠的神经元、星形胶质细胞及少突胶质细胞中，两者共同表达的易感基因数目较多；而在小胶质细胞和少突胶质前体细胞中，两者共同表达的易感基因数目少。此外，在人类脑组织单细胞特异表达的精神分裂症易感基因参与突触可塑性调控和钙离子信号转导等生物学过程。结论 ·精神分裂症易感基因在人类和小鼠脑组织单细胞水平的表达模式具有细胞类型的差异性，可为采用小鼠模型来研究精神分裂症病因学机制提供线索和依据。

关键词: 精神分裂症, 易感基因, 小鼠模型, 单细胞 RNA测序, 基因表达

Abstract:

Objective · To investigate the patterns of schizophrenia susceptibility genes in different neuronal cell types of human and mobrains. 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 mobrains were used to explore the 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 analyzedfunctional annotation tools the DAVID database. Results · Comparisons were made about single cell RNA-seq data between human and mobrains, and there existed distinct patterns of schizophrenia susceptibility genes across species. Neurons, astrocytes and oligodendrocytes both human and mowere shown to have more co-expressed schizophrenia susceptibility genes, while co- 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 profiles at the single cell level in human and mobrains, which provides clues and evidence for revealing the etiological mechanism of schizophrenia based on momodel research.

Key words: schizophrenia, susceptibility gene, momodel, single cell RNA-seq, gene

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