Antunes André S L M, Martins-de-Souza Daniel
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Experimental Medicine Research Cluster, University of Campinas, Campinas, Brazil.
Biol Psychiatry Glob Open Sci. 2022 Apr 6;3(3):329-339. doi: 10.1016/j.bpsgos.2022.03.013. eCollection 2023 Jul.
Neuroscience is currently one of the most challenging research fields owing to the enormous complexity of the mammalian nervous system. We are yet to understand precise transcriptional programs that govern cell fate during neurodevelopment, resolve the connectome of the mammalian brain, and determine the etiology of various neurodegenerative and psychiatric disorders. Technological advances in the past decade, notably single-cell RNA sequencing, have enabled huge progress in our understanding of such features. Our current knowledge of the transcriptome is largely derived from bulk RNA sequencing, which reveals only the average gene expression of millions of cells, potentially missing out on minor transcriptome differences between cells detectable only at single-cell resolution. Since 2009, several single-cell RNA sequencing techniques have emerged that enable the accurate classification of neuronal and glial cell subtypes beyond classical molecular markers and electrophysiological features and allow the identification of previously unknown cell types. Furthermore, it enables the interrogation of molecular and disease-relevant mechanisms and offers further possibilities for the discovery of new drug targets and disease biomarkers. This review intends to familiarize the reader with the main single-cell RNA sequencing techniques developed throughout the past decade and discusses their application in the fields of brain cell taxonomy, neurodevelopment, and psychiatric disorders.
由于哺乳动物神经系统极其复杂，神经科学目前是最具挑战性的研究领域之一。我们尚未了解在神经发育过程中控制细胞命运的精确转录程序，尚未解析哺乳动物大脑的连接组，也尚未确定各种神经退行性疾病和精神疾病的病因。过去十年的技术进步，尤其是单细胞RNA测序，使我们在理解这些特征方面取得了巨大进展。我们目前对转录组的了解很大程度上来自批量RNA测序，它只能揭示数百万个细胞的平均基因表达，可能会遗漏仅在单细胞分辨率下才能检测到的细胞间微小转录组差异。自2009年以来，出现了几种单细胞RNA测序技术，这些技术能够超越经典分子标记和电生理特征，对神经元和神经胶质细胞亚型进行准确分类，并能够识别以前未知的细胞类型。此外，它还能探究分子和疾病相关机制，并为发现新的药物靶点和疾病生物标志物提供更多可能性。这篇综述旨在让读者熟悉过去十年中开发的主要单细胞RNA测序技术，并讨论它们在脑细胞分类学、神经发育和精神疾病领域的应用。
