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A multimodal atlas of human brain cell types

人脑细胞类型的多模式图谱

基本信息

批准号：
9750113
负责人：
Ed Lein
金额：
$ 389.06万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-20 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9750113
关键词：
3-Dimensional Adult Affect Amygdaloid structure Anatomy Animal Model Atlases Autopsy Biophysics Brain Brain Diseases Brain Stem Brain region Cell Nucleus Cell physiology Cells Cellular Morphology Cellular Structures Censuses Cerebellum Classification Clinical Clinical Research Cognition Communities Complex Computing Methodologies Corpus striatum structure Data Data Set Databases Development Disease Electrophysiology (science)Elements Epilepsy Excision Fluorescent in Situ Hybridization Foundations Functional disorder Gene Expression Profile Gold Hippocampus (Brain)Hodgkin-Huxley model Human Hypothalamic structure Image Individual Injury Institutes International Maps Measures Methodology Methods Midbrain structure Modality Modeling Molecular Molecular Abnormality Morphology Mus Neocortex Neurons Neurosciences Organ Outcome Output Perception Phenotype Physiological Physiology Preparation Property Resected Resolution Role Sampling Science Site Slice Spatial Distribution Spinal Cord Standardization Structure Subcellular Anatomy Survey Methodology Surveys Taxonomy Techniques Thalamic structure Tissues Trauma Work base biophysical model brain cell brain tissue cell type collaboratory data resource human model human tissue multimodality neuronal circuitry neurosurgery patch clamp scale up single cell analysis single molecule single-cell RNA sequencing tool transcriptome transcriptome sequencing transcriptomics tumor

项目摘要

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.

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