Comparative Genomics of Precursor Diversity and Function

前体多样性和功能的比较基因组学

基本信息

批准号：
10375401
负责人：
Tarik F Haydar
金额：
$ 66.37万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10375401
关键词：
Age Apical Archives Bioinformatics Brain Candidate Disease Gene Cell Nucleus Cell division Cell physiology Cells Cerebral cortex Comparative Study Complement Complex Data Data Set Development Elements Embryo Evolution Factor Analysis Freezing Gene Expression Gene set enrichment analysis Genes Genomics Growth Human Imaging Techniques Immunohistochemistry In Situ Hybridization Individual Label Lead Macaca Macaca mulatta Mammals Maps Molecular Motor Mus Nature Neocortex Neuroglia Neurons Pan Genus Pattern Population Primates Process Property Radial Reporting Resolution Rodent Role Sampling Sensory Signal Pathway Small Nuclear RNA Specimen System Testing Time Ventricular Work cell behavior cell type comparative genomics deep sequencing executive function experimental study fetal genomic signature imaging modality in vivo lissencephaly molecular imaging neocortical nerve stem cell nervous system disorder neurogenesis nonhuman primate novel prenatal progenitor programs relating to nervous system sample archive single-cell RNA sequencing stem stem cells subventricular zone tissue archive tool transcriptome transcriptome sequencing transcriptomics

项目摘要

ABSTRACT The neocortex is the most complex cellular system in the natural world, the seat of motor, sensory and executive function. While many of the mechanisms responsible for neocortical formation are known, key aspects of how gene expression and cellular behavior lead to species-specific features of the neocortex remain to be discovered. Recent advances in genomic analysis and in vivo cellular labeling enable study of cortical development at an unprecedented level of resolution. In particular, some human-specific genes and neural precursor cells have been detected and current evidence suggests that increased proliferative capacity and longer neurogenesis times enable the expanded growth of the primate neocortex. In this project using archived tissue, we will comprehensively compare the heterogeneous groups of neural precursor cells in mouse, macaque, chimpanzee and human neocortex. Using single cell and single nucleus RNA sequencing and implementation of novel molecular labeling tools, we will compare genomic signatures and in vivo behavior of these cells to uncover mechanisms of brain growth and evolution. A significant focus of this project will be on a precursor type called the basal radial glial cell (bRGC), thought to have emerged recently in evolution to enable expansion of the primate brain. However, our preliminary experiments uncover multiple groups of bRGCs in mouse neocortex that share key features of bRGCs found in primate brain, contradicting reports suggesting their biased role in primate brain growth. These studies will use emerging evidence and new tools to elucidate species-specific programs controlling neocortical growth.

抽象的新皮质是自然界中最复杂的细胞系统，是运动、感觉和感觉的所在地。执行职能。虽然许多负责新皮质形成的机制是已知的，但关键基因表达和细胞行为如何导致新皮质的物种特异性特征的一些方面仍然存在被发现。基因组分析和体内细胞标记的最新进展使得皮质研究成为可能以前所未有的分辨率发展。特别是一些人类特有的基因和神经已检测到前体细胞，目前的证据表明增殖能力和较长的神经发生时间使灵长类新皮质的生长得以扩大。在这个项目中使用存档的组织，我们将全面比较神经前体细胞的异质群体小鼠、猕猴、黑猩猩和人类新皮质。使用单细胞和单核 RNA 测序和新型分子标记工具的实施，我们将比较基因组特征和体内行为这些细胞来揭示大脑生长和进化的机制。该项目的一个重要重点将是一种称为基底放射状胶质细胞（bRGC）的前体类型，被认为是最近在进化过程中出现的使灵长类动物的大脑得以扩展。然而，我们的初步实验揭示了多组小鼠新皮质中的 bRGC 与灵长类动物大脑中发现的 bRGC 具有相同的关键特征，这与报道相矛盾这表明它们在灵长类动物大脑生长中的作用存在偏差。这些研究将使用新出现的证据和新工具阐明控制新皮质生长的物种特异性程序。