Epigenomic Approaches for Unbiased Single Human-Neuron Subtype Census

摘要 了解大脑区域的确切细胞类型组成是尝试整合时的基本步骤 生理、行为、神经化学和分子数据。目前，虽然主要的细胞类型- 存在于皮质中的类型已经通过少数特定的标记物来定义， 这些类别及其位置和连通性远未得到了解。DNA甲基化（mC）是一种 在有丝分裂后的细胞中持续存在的稳定共价修饰， 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， 在啮齿类动物和人类皮层中，以及区分小鼠皮层中的神经元类型。然而， 已知是什么识别了属于大脑区域内特定类别的神经元群体，例如， 不同皮层层或额叶皮层区域的锥体神经元。该项目建议开发 必要的技术，以解决在皮层特定的单神经元mC地图的挑战， 用人类死后的额叶皮层组织这种方法的推广将最终导致 对人脑中所有神经元类型进行了彻底的分类。

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.