Tabular Data from "Single-cell transcriptomic and proteomic analysis of Parkinson's disease brains"

Tabular Data from the publication Single-cell transcriptomic and proteomic analysis of Parkinson's disease brains (Zhu et al, Sci. Tranl. Med. 2024). Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and recent evidence suggests that pathogenesis may be in part mediated by inflammatory processes, the molecular and cellular architectures of which are largely unknown. To identify and characterize selectively vulnerable brain cell populations in PD, we performed single-nucleus transcriptomics and unbiased proteomics to profile the prefrontal cortex from postmortem human brains of six individuals with late-stage PD and six age-matched controls. Analysis of nearly 80,000 nuclei led to the identification of eight major brain cell types, including elevated brain-resident T cells in PD, each with distinct transcriptional changes in agreement with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem brain tissues, we found that α-synuclein pathology was inversely correlated with chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins in the prefrontal cortex that were preferentially down-regulated in PD. By comparing this single-cell PD dataset with a published analysis of similar brain regions in Alzheimer’s disease (AD), we found no common differentially expressed genes in neurons but identified many shared differentially expressed genes in glial cells, suggesting that the disease etiologies, especially in the context of neuronal vulnerability, in PD and AD are likely distinct.本数据集源自Zhu等人2024年发表于《科学·转化医学》（*Science Translational Medicine*）的论文《帕金森病大脑的单细胞转录组学与蛋白质组学分析》。帕金森病（Parkinson’s disease, PD）是一种高发的神经退行性疾病，现有研究证据表明其发病机制可能部分由炎症过程介导，但其相关的分子与细胞架构在很大程度上仍未明确。为鉴定并表征帕金森病中存在选择性易损性的大脑细胞群，本研究对6名晚期帕金森病患者与6名年龄匹配对照者的死后人类大脑前额叶皮层开展了单细胞核转录组学（single-nucleus transcriptomics）与无偏倚蛋白质组学（unbiased proteomics）分析。对近8万个细胞核的分析共鉴定出8种主要大脑细胞类型，其中帕金森病患者脑内的脑驻留T细胞比例显著升高，各类细胞均出现与帕金森病已知遗传学特征相符的独特转录组改变。通过对同一死后脑组织中的路易体病理进行分析，本研究发现兴奋性神经元内的α-突触核蛋白（α-synuclein）病理负荷与伴侣蛋白表达呈负相关关系。在分析细胞间互作时，本研究发现神经元-星形胶质细胞（astrocyte）的互作出现选择性减弱，同时神经炎症反应增强。对同一大脑样本的蛋白质组学分析显示，前额叶皮层内的突触蛋白在帕金森病中呈现优先下调趋势。通过将本单细胞帕金森病数据集与已发表的阿尔茨海默病（Alzheimer’s disease, AD）相似脑区分析数据进行对比，本研究发现神经元中不存在共同的差异表达基因，但在胶质细胞（glial cells）中鉴定出大量共享的差异表达基因，这表明帕金森病与阿尔茨海默病的发病病因——尤其是在神经元易损性层面——很可能存在显著差异。