Epigenomic Approaches for Unbiased Single Human-Neuron Subtype Census

无偏见的单个人类神经元亚型普查的表观基因组方法

• 批准号: 9228115
• 负责人: M MARGARITA BEHRENS
• 金额: $ 29.1万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-28 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9228115
• 关键词: Address; Adult; Animal Model; Antibodies; Area; Autopsy; BRAIN initiative; Behavioral; Brain; Brain region; Cataloging; Catalogs; Categories; Cell Nucleus; Cells; Censuses; Characteristics; Classification; Cluster Analysis; DNA Methylation; Data; Dependence; Development; Flow Cytometry; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Goals; High-Throughput RNA Sequencing; Human; Immunohistochemistry; Lead; Location; Maps; Mental disorders; Methodology; Methods; Mitotic; Modification; Molecular; Morphology; Mus; Nature; Neuraxis; Neuroglia; Neurons; Neurotransmitters; Nuclear Proteins; Pattern; Physiological; Pilot Projects; Population; Recording of previous events; Rodent; Sampling; Sorting - Cell Movement; Techniques; Technology; Tissues; Translating; abstracting; base; cell type; combinatorial; epigenomics; excitatory neuron; frontal lobe; hippocampal pyramidal neuron; human tissue; improved; inhibitory neuron; method development; methylation pattern; neurochemistry; public health relevance

Abstract Understanding the exact cell-type composition in brain regions is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of cell- types present in cortex have been defined through a handful of specific markers, the different subtypes within these categories, as well as their location and connectivity are far from understood. DNA methylation (mC) is a stable covalent modification that persists in post-mitotic cells throughout their lifetime, defining their cellular identity. Methylation patterns are cell type specific, differentiating the major types of cells i.e., neurons and glia, in the rodent and human cortex, as well as differentiating neuronal types in mouse cortex. However, little is known about what identifies the populations of neurons belonging specific categories within a brain region e.g. pyramidal neurons in different cortical layers or areas of frontal cortex. This project proposes to develop the technology necessary to address the challenge of producing single-neuron mC maps in a cortical layer-specific manner using human postmortem frontal-cortex tissue. Expansion of this methodology will ultimately lead to a thorough classification of all neuronal types in the human brain.

抽象的 了解大脑区域的确切细胞类型组成是尝试整合的基本步骤 生理、行为、神经化学和分子数据。目前，虽然细胞的主要类别 皮层中存在的类型已通过一些特定标记来定义，其中的不同亚型 这些类别及其位置和连接性尚不清楚。 DNA 甲基化 (mC) 是 稳定的共价修饰在有丝分裂后细胞的整个一生中持续存在，定义了它们的细胞 身份。甲基化模式是细胞类型特异性的，区分主要类型的细胞，即神经元和神经胶质细胞， 在啮齿动物和人类皮质中，以及区分小鼠皮质中的神经元类型。然而，很少的是 了解如何识别大脑区域内属于特定类别的神经元群体，例如 不同皮质层或额叶皮质区域的锥体神经元。本项目拟开发 解决在特定皮质层中生成单神经元 mC 图的挑战所必需的技术 使用人类死后额叶皮质组织的方式。这种方法的扩展最终将导致 对人脑中所有神经元类型进行彻底分类。