A multimodal atlas of human brain cell types

摘要： 人脑细胞类型的多模式图谱 细胞类型是大脑的组成部分，包括形成特定神经元的神经元类型 负责感知、认知和行动的电路，以及执行其他功能的非神经元元件 正常大脑功能的重要作用。深入了解细胞类型对于了解大脑至关重要 结构和功能，以及疾病和损伤中功能障碍的机制，一般来说 通过潜在的遗传异常或选择性地影响特定的细胞成分 容易受到侮辱和伤害。尽管细胞类型的重要性显而易见，但我们对其的了解 多样性、特定属性和离散性是非常不完整的。这在人脑中尤其如此， 由于技术限制、无法获取活体脑组织以及其庞大的规模和复杂性， 阻碍进展；然而，一套新的分子、解剖学和生理学工具和技术正在出现。 现在可以在模型生物和人类的脑组织中发挥作用。标准化和规模化 这些技术通过提供对领域的广泛而深入的理解而极大地改变了该领域 人类大脑的组成部分及其保守和独特的功能。 我们在此提议组建一个由单细胞领域世界领导者组成的跨学科联盟 转录组学、人类细胞生理学和解剖学以及神经元建模，以创建全面的 人类脑细胞类型图谱作为社区数据资源。该图谱的基础是分子 基于大规模单细胞转录组学的细胞类型分类，结合对细胞的广泛调查 整个大脑和脊髓的类型，对新皮质和海马体、区域进行深入分析 其中可以分析活体神经外科切除细胞的功能和解剖特性。 这些分子细胞类型的分布将使用单分子在组织切片上绘制 多重荧光原位杂交对不同大脑区域的细胞类型进行定量普查。 为了了解这些分子细胞类型的特性，我们将在整个联盟中标准化方法 由人体切片膜片钳电生理学专家组成，研究其结构、功能和分子 皮质细胞类型的特性。最后，我们将推导出对细胞类型进行分类、进行神经元建模的工具 了解和预测细胞类型的功能，并比较小鼠和小鼠之间的细胞类型特性 人类。结果将是第一个详细的人类脑细胞类型和发育的图谱 人脑研究的标准化方法可能会促进基础和临床的快速进展 神经科学。

Abstract: A Multimodal Atlas of Human Brain Cell Types Cell types are the building blocks of the brain, including the neuron types forming specific neuronal circuits responsible for perception, cognition and action, and the non-neuronal elements performing other essential roles for proper brain function. A deep understanding of cell types is essential to understand brain structure and function, as well as mechanisms underlying dysfunction in disorders and injury, which in general affect specific cellular components either through underlying genetic abnormalities or through selective vulnerability to insults and injury. Despite the obvious importance of cell types, our understanding of their diversity, specific properties and discreteness is highly incomplete. This is particularly true in the human brain, where technological limitations, lack of access to living brain tissues, and the sheer size and complexity has hampered progress; however, a new set of molecular, anatomical and physiological tools and techniques are now available that work in brain tissue both from model organisms and human. Standardization and scale-up of these techniques offers to dramatically change the field by providing a broad and deep understanding of the building blocks of the human brain, and their conserved and unique features. We propose here to bring together an interdisciplinary consortium of world leaders in single cell transcriptomics, human cellular physiology and anatomy, and neuronal modeling to create a comprehensive atlas of human brain cell types as a community data resource. The foundation of this atlas is a molecular classification of cell types based on large-scale single cell transcriptomics, combining a broad survey of cell types across the entire brain and spinal cord with a deep analysis of the neocortex and hippocampus, regions in which it is possible to analyze functional and anatomical properties of cells in living neurosurgical resections. The distribution of these molecular cell types will be mapped on tissue sections using single molecular multiplex fluorescent in situ hybridization to create a quantitative census of cell types in different brain regions. To understand the properties of these molecular cell types, we will standardize methods across a consortium of experts in human slice patch clamp electrophysiology to study the structure, function and molecular properties of cortical cell types. Finally, we will derive tools to classify cell types, perform neuronal modeling to understand and predict the function of cell types, and compare cell type properties between mouse and human. The outcome will be the first detailed atlas of human brain cell types and the development of standardized methods for human brain study that are likely to catalyze rapid progress in basic and clinical neuroscience.