Alvarado Chelsea X, Weller Cory A, Johnson Nicholas, Leonard Hampton L, Singleton Andrew B, Reed Xylena, Blauewendraat Cornelis, Nalls Mike A
National Institute on Aging.
Res Sq. 2023 Nov 15:rs.3.rs-3390225. doi: 10.21203/rs.3.rs-3390225/v1.
Single-cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression.
To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single-cell sequencing data, and bulk expression studies in a diverse series of brain region tissues.
We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Subsequently, putative roles of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis were identified.
We have helped refine the genetic regions and cell types effected across multiple neurodegenerative diseases, helping focus future translational research efforts.
单细胞RNA测序为阐明疾病的复杂基础打开了一扇窗口，尤其是在量化组织和细胞类型特异性基因表达的相关性方面。
为了确定在整个神经退行性疾病谱系中对治疗靶点开发重要的细胞类型和基因，我们利用了全基因组关联研究、近期的单细胞测序数据以及一系列不同脑区组织中的大量表达研究。
我们能够在三种主要的神经退行性疾病（阿尔茨海默病、肌萎缩侧索硬化症和帕金森病）的大脑中识别出与免疫相关的重要细胞类型。随后，确定了30个精细定位位点在多种神经退行性疾病及其发病机制中涉及7个基因的假定作用。
我们有助于完善多种神经退行性疾病所影响的遗传区域和细胞类型，有助于集中未来的转化研究工作。
