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: 10266105
• 负责人: NENAD SESTAN
• 金额: $ 112.84万
• 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/10266105
• 关键词: Adopted; Adult; Affect; Age; Anatomy; 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; Gene Expression Profile; Generations; 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; tissue archive; 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.

摘要 人脑是一个高度复杂的生物组织，由数百个区域组成， 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 神经回路是我们心智能力的基础，如果功能失调，就会导致神经和精神疾病。 因此，开发这些细胞类型的图谱以及它们彼此之间的差异是至关重要的， 了解人类大脑发育和功能的生物学过程。另外由于 脑及其组成细胞的一般细胞结构在灵长类动物中通常是保守的， 了解这些细胞类型在物种之间的差异对于了解人类的独特性也是至关重要的 认知和行为方面。因此，我们建议使用单细胞转录组学来严格定义 涉及高级认知和行为的十个大脑区域中的细胞类型和状态，以及五个关键区域中的细胞类型和状态。 人类、黑猩猩（我们现存的近亲之一）、恒河猴（ 最常被研究的旧世界非人类灵长类动物）和普通绒猴（一种新兴的新世界非人类灵长类动物）。 人灵长类动物模型系统）。通过生成、分析这些数据，并将其与现有的未发布的 数据集，我们建议开发一个人类和非人类灵长类动物细胞图谱，并确定共享和分歧 分子和细胞特征跨越物种，地区和年龄。此外，我们还将验证 该图谱包括分子特征，并创建了一个数据可视化和传播门户。