Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer's disease.
Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer's disease.
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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图谱。
DOI：
10.1038/s41593-022-01251-x
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发表时间：
2023
影响因子：
25
通讯作者：
Wang,Xiao
中科院分区：
文献类型：
--
作者：
Zeng,Hu;Huang,Jiahao;Zhou,Haowen;Meilandt,WilliamJ;Dejanovic,Borislav;Zhou,Yiming;Bohlen,ChristopherJ;Lee,Seung-Hye;Ren,Jingyi;Liu,Albert;Tang,Zefang;Sheng,Hao;Liu,Jia;Sheng,Morgan;Wang,Xiao
复杂疾病的特点是时空细胞和分子的变化，可能难以全面捕捉。然而，了解病理学的时空动力学基础可以揭示疾病的机制和进展。在这里，我们介绍STARmap PLUS，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，我们分析了8个月和13个月大的阿尔茨海默病小鼠模型的脑组织。我们的方法提供了一个全面的疾病进展的细胞图谱。它揭示了一种核-壳结构，其中疾病相关的小胶质细胞（DAM）紧密接触淀粉样蛋白-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CA 1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方法将单细胞基因表达谱与亚细胞分辨率的组织组织病理学联系起来，提供了一种工具来确定病理学基础的分子和细胞变化。
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.