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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的人脑是一个高度复杂的生物组织，由无数个区域组成，分为数百个区域。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理能力的基础，当功能失调时，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之间的差异对于了解人类大脑发育和功能的生物过程。另外，因为大脑的一般细胞结构及其组成细胞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有何不同对于理解人类的独特之处也至关重要认知和行为方面。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以及五个关键区域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（猕猴）的发育时间点最常研究的旧世界非人类灵长类动物）和普通狨猴（一种新兴的新世界非人类灵长类动物）人类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未发布的数据集成数据集，我们建议开发人类和非人类灵长类动物细胞图谱，并识别共享和分歧的细胞图谱跨物种、地区和年龄的分子和细胞特征。此外，我们将验证以下关键方面该图集包括分子特征，并创建一个数据可视化和传播门户。