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 正常的大脑功能所必需的角色。深入了解细胞类型是了解大脑的关键 结构和功能，以及障碍和损伤的潜在功能障碍的机制，这些通常 通过潜在的遗传异常或选择性地影响特定的细胞成分 易受侮辱和伤害。尽管细胞类型显然很重要，但我们对它们的理解 多样性、特殊性和离散性是高度不完整的。这在人脑中尤其如此， 在那里，技术限制，无法获得活的脑组织，以及纯粹的大小和复杂性 阻碍了进展；然而，一套新的分子、解剖学和生理学工具和技术 现在可以在模型生物和人类的脑组织中使用。标准化和放大 这些技术提供了广泛而深入的理解，从而极大地改变了这个领域 人类大脑的组成部分，以及它们保守而独特的特征。 我们建议在这里将一个由世界领导人组成的跨学科联盟聚集在一起 转录学，人体细胞生理学和解剖学，以及神经元建模，以创建全面的 作为社区数据资源的人脑细胞类型图集。这本地图集的基础是一个分子 基于大规模单细胞转录的细胞类型分类，结合对细胞的广泛调查 跨整个大脑和脊髓的类型，以及对新皮质和海马体区域的深入分析 其中可以分析活的神经外科手术切除的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绘制在组织切片上 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属性，我们将跨联盟标准化方法 由人类切片膜片钳电生理学专家研究其结构、功能和分子 皮质细胞类型的属性。最后，我们将派生工具来分类细胞类型，执行神经元建模以 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发展 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.