Here we demonstrate a technique to generate proteomic signatures of specific cell types within heterogeneous populations. While our method is broadly applicable across biological systems, we have limited the current work to study neural cell types isolated from human, post-mortem Alzheimer's disease (AD) and aged-matched non-symptomatic (NS) brains. Motivating the need for this tool, we conducted an initial meta-analysis of current, human AD proteomics studies. While the results broadly corroborated major neurodegenerative disease hypotheses, cell type-specific predictions were limited. By adapting our Formaldehyde-fixed Intracellular Target-Sorted Antigen Retrieval (FITSAR) method for proteomics and applying this technique to characterize AD and NS brains, we generated enriched neuron and astrocyte proteomic profiles for a sample set of donors (available at www.fitsarpro.appspot.com). Results showed the feasibility for using FITSAR to evaluate cell-type specific hypotheses. Our overall methodological approach provides an accessible platform to determine protein presence in specific cell types and emphasizes the need for protein-compatible techniques to resolve systems complicated by cellular heterogeneity.

中文翻译：

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从无症状和患病组织中生成细胞类型特异性蛋白质特征。


在这里，我们展示了一种在异质群体中生成特定细胞类型的蛋白质组特征的技术。虽然我们的方法广泛适用于整个生物系统，但我们目前的工作仅限于研究从人类死后阿尔茨海默病（AD）和年龄匹配的无症状（NS）大脑中分离的神经细胞类型。为了激发对该工具的需求，我们对当前的人类 AD 蛋白质组学研究进行了初步荟萃分析。虽然结果广泛证实了主要的神经退行性疾病假设，但细胞类型特异性的预测是有限的。通过采用我们的甲醛固定细胞内目标排序抗原检索 (FITSAR) 方法进行蛋白质组学，并应用该技术来表征 AD 和 NS 大脑，我们为一组供体样本生成了丰富的神经元和星形胶质细胞蛋白质组图谱（可在 www.fitsarpro 获取）。 appspot.com）。结果表明使用 FITSAR 评估细胞类型特定假设的可行性。我们的整体方法提供了一个可访问的平台来确定特定细胞类型中蛋白质的存在，并强调需要蛋白质兼容的技术来解决细胞异质性复杂的系统。