单细胞测序在神经精神疾病研究及未来精准诊疗中的应用

摘要/Abstract

摘要： 大多数神经精神疾病的病因复杂，病理机制研究难度大，相应药物或疗法的研发进展十分有限，因此在诊断及治疗方面都面临着巨大的未满足的临床需求。这一困境部分可归结于大脑各区域中细胞类型的多样性和高度异质性。以往对于神经精神疾病的研究主要基于解剖学、组织学、神经电生理或在细胞群体水平进行的传统测序等技术，无法在细胞亚型或单细胞水平开展转录组分析，从而鉴定神经细胞在各种神经精神疾病中的病理性改变。近年来，单细胞测序技术的快速发展为该领域相关研究提供了新的思路和手段。单细胞转录组测序可以测定单个细胞的基因表达图谱，从而可能鉴定出新的疾病关联细胞亚型，同时可以在同一疾病条件下比较各个细胞亚群的数目变化及各亚群内转录组水平的改变，从而有力推动了神经精神疾病发病机制的探索、疾病分型的重新定义、治疗新靶点的发现。本研究从阿尔兹海默症等几种重要神经精神疾病的发病机制研究角度，对单细胞转录组测序技术在神经精神疾病中的应用进展进行综述，并展望该技术体系在未来精准诊断和治疗中的应用前景。

关键词: font-size:medium, ">单细胞转录组测序；神经精神疾病；细胞图谱；精准医疗

Abstract: Neuropsychiatric diseases are a range of highly heterogeneous disorders， with common characteristics including unknown etiology， repetitive course， and significant burden.The diversity， heterogeneity， and uniqueness of the cell types in the different regions and layers in the brain caused great difficulties to understand the molecular mechanisms in the pathology of neuropsychiatric diseases， hence there are significant unmet medical needs.Cells in the nervous system have previously been classified using location， histology or bulk RNA sequencing at population level. But none of these approaches convey sufficient information to illustrate the diversity of brain cells or to provide insights into cellular susceptibilities in neuropsychiatric diseases.The single-cell RNA sequencing (scRNA-seq) technologies have been developed over the past decade. It enables characterization of gene expression profiles at single-cell level， thus allows identification of novel cellular subtypes， and comparison of different cell populations and cellular states in the context of neuropsychiatric disease. This technology will greatly advance our understanding of the molecular and cellular mechanisms underlying neuropsychiatric diseases， may lead to revised classification of cell types， and may reveal novel therapeutic targets. This article reviewed recent progress of the application of scRNA-seq in the studies on neuropsychiatric diseases， from building cellular atlas of the brain to the investigation of mechanisms underlying neuropsychiatric diseases， and discussed its application prospects in precise diagnosis and treatment of neuropsychiatric diseases.

Key words: font-size:medium, ">Single-cell RNA sequencing, Neuropsychiatric diseases, Cellular atlas, Precision medicine

中图分类号:

张晓琳, 王卫娣, 周子凯. 单细胞测序在神经精神疾病研究及未来精准诊疗中的应用[J]. 中国医药导刊, 2022, 24(3): 211-218.

ZHANG Xiaolin, WANG Weidi, ZHOU Zikai. Application of Single-cell RNA Sequencing in Studies on Neuropsychiatric Diseases and Its Prospects in Precision Medicine[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2022, 24(3): 211-218.

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