Developmental cell census of human and non-human primate brain

摘要 人脑是一个高度复杂的生物组织，由数以百计的区域组成 指具有不同分子、形态和生理特性的细胞类型。这些单元格及其关联 回路是我们心智能力的基础，当功能失调时，会导致神经和精神障碍。 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学过程。另外，因为 在灵长类动物中，大脑的一般细胞结构及其组成细胞通常都是保守的， 了解这些细胞类型在不同物种之间的差异对于理解独特的人类也是至关重要的 认知和行为的各方面。因此，我们建议使用单细胞转录切割法来严格定义 与较高认知和行为有关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( 最常被研究的东半球非人类灵长类动物)和常见的绒猴(一种新兴的新大陆非人类灵长类动物) 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的未发布数据集成 数据集，我们建议开发一个人类和非人类灵长类细胞图谱，并识别共享和分歧 跨物种、地区和年龄的分子和细胞特征。此外，我们还将验证以下关键方面 这份地图集包括分子签名，并创建了一个数据可视化和传播门户。

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 By generating, analyzing, and integrating these data with existing unpublished datasets, we propose to develop a human and non-human primate cell atlas and identify shared and divergent molecular and cellular features across species,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.