Comparative Genomics of Precursor Diversity and Function

摘要 新皮质是自然界中最复杂的细胞系统，是运动、感觉和 执行职能。虽然许多负责新皮质形成的机制是已知的，但关键是 基因表达和细胞行为如何导致新大脑皮层物种特有特征的方面仍然存在 等着被发现。基因组分析和活体细胞标记的最新进展使皮质细胞的研究成为可能 以前所未有的决心发展。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，增殖能力增加和 较长的神经发生时间可以扩大灵长类新皮质的生长。在此项目中使用 存档的组织，我们将全面比较神经前体细胞的异质性群 老鼠、猕猴、黑猩猩和人类大脑皮层。利用单细胞和单核RNA测序 和实施新的分子标记工具，我们将比较基因组签名和体内行为 以揭示大脑生长和进化的机制。该项目的一个重要焦点将是 在一种称为基底径向胶质细胞(BRGC)的前体类型上，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张。然而，我们的初步实验发现了多组 小鼠新皮质中的bRGCs与灵长类动物大脑中发现的bRGCs的关键特征相同，这与报道相矛盾 这表明它们在灵长类大脑发育中的偏颇作用。这些研究将使用新的证据和新的工具 阐明控制新皮质生长的物种特异性程序。

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.