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新方法实现阿尔茨海默病小鼠模型中单细胞转录状态和组织病理学的综合原位定位
作者:小柯机器人 发布时间:2023/2/5 11:12:07

美国麻省理工学院Xiao Wang等研究人员合作实现阿尔茨海默病小鼠模型中单细胞转录状态和组织病理学的综合原位定位。相关论文于2023年2月2日在线发表于国际学术期刊《自然—神经科学》。

研究人员报道了STARmap PLUS,这是一种将高分辨率空间转录组学与同一组织切片中的蛋白质检测相结合的方法。作为原理的证明,研究人员人员分析了8个月和13个月大的阿尔茨海默病小鼠模型的脑组织。这个方法提供了疾病进展的全面细胞地图。它揭示了一种核壳结构,其中疾病相关的小胶质细胞(DAM)密切接触淀粉样β斑块,而疾病相关的星形胶质细胞样(DAA样)细胞和少突胶质细胞前体细胞(OPC)富集在斑块-DAM复合物周围的外壳中。过度磷酸化的tau蛋白主要出现在CA1区的兴奋性神经元中,并与少突胶质细胞亚型的局部富集相关。STARmap PLUS方法在亚细胞分辨率下将单细胞基因表达谱与组织组织病理学连接起来,提供了一种精确定位病理基础的分子和细胞变化的工具。

据介绍,复杂疾病的特征是细胞和分子的时空变化,可能难以全面捕捉。然而,了解病理背后的时空动态可以揭示疾病的机制和进展。

附:英文原文

Title: Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease

Author: Zeng, Hu, Huang, Jiahao, Zhou, Haowen, Meilandt, William J., Dejanovic, Borislav, Zhou, Yiming, Bohlen, Christopher J., Lee, Seung-Hye, Ren, Jingyi, Liu, Albert, Tang, Zefang, Sheng, Hao, Liu, Jia, Sheng, Morgan, Wang, Xiao

Issue&Volume: 2023-02-02

Abstract: Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can shed light on disease mechanisms and progression. Here we introduce STARmap PLUS, a method that combines high-resolution spatial transcriptomics with protein detection in the same tissue section. As proof of principle, we analyze brain tissues of a mouse model of Alzheimer’s disease at 8 and 13 months of age. Our approach provides a comprehensive cellular map of disease progression. It reveals a core–shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocyte-like (DAA-like) cells and oligodendrocyte precursor cells (OPCs) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerges mainly in excitatory neurons in the CA1 region and correlates with the local enrichment of oligodendrocyte subtypes. The STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing a tool to pinpoint the molecular and cellular changes underlying pathology.

DOI: 10.1038/s41593-022-01251-x

Source: https://www.nature.com/articles/s41593-022-01251-x

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex