A multimodal atlas of human brain cell types

摘要： 人脑细胞类型的多模态图谱 细胞类型是大脑的构建块，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，以及执行其他任务的非神经元元件 对大脑正常功能至关重要。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潜在机制， 通过潜在的遗传异常或通过选择性的 易受侮辱和伤害。尽管细胞类型的重要性显而易见，但我们对它们的理解 多样性、具体属性和离散性是高度不完整的。这在人类大脑中尤其如此， 由于技术的限制，无法获取活体脑组织，再加上其庞大的规模和复杂性， 阻碍了进展;然而，一套新的分子，解剖和生理工具和技术， 现在可以在模型生物和人类的脑组织中工作。标准化和扩大规模 这些技术提供了一个广泛而深刻的理解， 人类大脑的组成部分，以及它们保守而独特的特征。 我们在这里提议，将单细胞领域的世界领导者组成一个跨学科联盟， 转录组学，人类细胞生理学和解剖学，以及神经元建模，以创建一个全面的 人类脑细胞类型图谱作为社区数据资源。这个图谱的基础是一个分子 基于大规模单细胞转录组学的细胞类型分类，结合细胞分类的广泛调查， 通过深入分析新皮层和海马体， 其中可以分析活体神经外科切除中细胞的功能和解剖学特性。 这些分子细胞类型的分布将使用单分子标记在组织切片上作图。 多重荧光原位杂交，以创建不同脑区细胞类型的定量普查。 为了了解这些分子细胞类型的特性，我们将在一个联盟中标准化方法。 的专家在人体切片膜片钳电生理学研究的结构，功能和分子 皮质细胞类型的特性。最后，我们将获得工具来分类细胞类型，执行神经元建模， 了解和预测细胞类型的功能，并比较小鼠和 人类结果将是第一个详细的人类脑细胞类型和发展的地图集。 人类大脑研究的标准化方法，可能会促进基础和临床研究的快速进展。 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.