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.

摘要