Developmental cell census of human and non-human primate brain

人类和非人类灵长类动物大脑的发育细胞普查

• 批准号: 10088878
• 负责人: NENAD SESTAN
• 金额: $ 120.81万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-17 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10088878
• 关键词: Adopted; Adult; Affect; Age; Anatomy; Archives; Area; Atlases; Behavior; Behavioral; Biological; Biological Models; Biological Process; Brain; Brain region; Callithrix; Callithrix jacchus jacchus; Cell Nucleus; Cells; Censuses; Cognition; Cognitive; Collection; Communities; Complement; Complex; Corpus striatum structure; Data; Data Set; Databases; Deposition; Development; Ethics; Female; Freezing; Generations; Genetic Transcription; Genomics; Guidelines; Human; Human Development; Joints; Knowledge; Lead; Macaca; Macaca mulatta; Measures; Medial; Medial Dorsal Nucleus; Mental disorders; Methods; Modeling; Molecular; Molecular Profiling; Morphology; Motor Cortex; Neonatal; Pan Genus; Phase; Physiological; Play; Prefrontal Cortex; Primates; Production; Property; Psyche structure; Research; Resources; Role; Small Nuclear RNA; Specimen; Standardization; Structure; Surveys; System; Taxonomy; Technology; Thalamic structure; Tissues; Validation; Work; analytical tool; brain cell; cell type; data dissemination; data integration; data quality; data resource; data sharing; data visualization; dentate gyrus; early childhood; entorhinal cortex; experimental study; fetal; frontal lobe; genomic data; hippocampal subregions; human data; human fetus tissue; infancy; male; nervous system disorder; nonhuman primate; postnatal; prenatal; sex; social; tool; transcriptome sequencing; transcriptomics

ABSTRACT The human brain is a highly complex biological tissue organized into hundreds of regions composed of a myriad of cell types with distinct molecular, morphological, and physiological properties. These cells and their associated circuits underlie our mental abilities and, when dysfunctional, lead to neurological and psychiatric disorders. Consequently, developing an atlas of these cell types and how they differ from one another is essential for understanding the biological processes underlying human brain development and function. In addition, because both the general cytoarchitecture of the brain and its constituent cells are generally conserved across primates, knowledge of how these cell types differ between species is also essential for understanding uniquely human aspects of cognition and behavior. We therefore propose to use single cell transcriptomics to rigorously define cell types and states in ten brain regions involved in higher cognition and behavior and across five key developmental timepoints of human, chimpanzee (one of our closest extant relatives), rhesus macaque (the most commonly studied Old World non-human primate), and common marmoset (an emerging New World non- human primate model system). By generating, analyzing, and integrating these data with existing unpublished datasets, we propose to develop a human and non-human primate cell atlas and identify shared and divergent molecular and cellular features across species, regions, and ages. Furthermore, we will validate key aspects of this atlas, including molecular signatures, and create a data visualization and dissemination portal.

抽象的 人脑是一种高度复杂的生物组织，该组织组织成数百个由无数的区域组成 具有不同分子，形态和生理特性的细胞类型。这些细胞及其相关的 电路是我们的心理能力以及功能失调的导致神经和精神疾病的基础。 因此，开发这些细胞类型的地图集及其彼此之间的不同是必不可少的 了解人脑发育和功能的生物学过程。另外，因为 大脑及其成分细胞的一般细胞结构通常都是在灵长类动物之间保守的， 了解这些细胞类型之间如何差异的知识对于理解独特的人类也是必不可少的 认知和行为的各个方面。因此，我们建议使用单细胞转录组学严格定义 细胞类型和状态在较高认知和行为以及五个关键的十个大脑区域中 人类，黑猩猩（我们最亲密的亲戚之一）的发展时间点，恒河猴（ 最常见的旧世界非人类灵长类动物）和普通的玛格斯（一个新的世界非世界非人类的灵长类动物 人类灵长类动物模型系统）。通过生成，分析和集成这些数据与现有的未发表 数据集，我们建议开发人类和非人类的灵长类动物细胞地图集，并确定共享和分歧 物种，区域和年龄之间的分子和细胞特征。此外，我们将验证 该地图集，包括分子特征，并创建数据可视化和传播门户。