UC Irvine AD Translational Center for Disease Model Resources-Spatial Transcriptomics Supplement

项目摘要/摘要 围绕阿尔茨海默病(AD)的神经退行性疾病机制复杂，有 尽管发现了与以下疾病相关的风险因素和基因突变，但迄今仍在很大程度上未知 这种疾病。加州大学欧文模型-AD项目的主要目标之一是描述严谨、可重现的 以及阿尔茨海默病(AD)的可翻译动物模型研究，AD是最常见的神经退行性疾病 痴呆症。在这方面，利用高通量基因表达对阿尔茨海默病小鼠模型的深入表征 整体(rna-seq)和单细胞分辨率(单核rna-seq；nrna-seq)的研究有可能 揭开新的生物学和确定疾病的驱动因素，这是非常有治疗价值的。然而，当前的批量 而单核转录切分方法缺乏编码空间、大脑区域特定信息的能力， 它们对破译当地环境中的基因表达变化和解决长期存在的问题至关重要 阿尔茨海默病相关病理过程中神经细胞和神经胶质细胞基因表达如何变化的问题。 目前的项目通过采用全面的数据驱动方法，在该领域取得了重大进展 发现驻留神经细胞的空间组织及其在疾病进展过程中的变化 广告。最后，该项目将确定人类和小鼠模型系统之间的共享转录签名 以空间分辨的方式。

Project Summary/Abstract Neurodegenerative disease mechanisms encompassing Alzheimer’s disease (AD) are complex and have remained largely unknown to date despite the identification of risk factors and genetic mutations associated with the disease. One of the major goals of the UC Irvine MODEL-AD project is to characterize rigorous, reproducible and translatable animal model studies of Alzheimer’s disease (AD), the most common form of neurodegenerative dementia. In this respect, the deep characterization of mouse models of AD using high throughput gene-expression studies at bulk (RNA-seq) and single-cell resolutions (single-nuclei RNA-seq; snRNA-seq) have the potential to unravel novel biology and define drivers of the disease, which is of great therapeutic value. However, current bulk and single-nuclei transcriptomics approaches lack the ability to encode spatial, brain region-specific information, which are crucial to decipher gene-expression changes in the local environment and address long standing questions on how expression of neuronal and glial genes changes during progression of AD-related pathology. The current project represents a major advance in the field by taking a comprehensive approach to data-driven discovery to identify spatial organization of resident neural cells and how they change during the progression of AD. Finally, the project will identify shared transcriptomic signatures between human and mouse model systems in a spatially-resolved manner.