Spatial cell type mapping of multiple sclerosis lesions
Spatial cell type mapping of multiple sclerosis lesions
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多发性硬化症病变的空间细胞类型图谱
DOI：
10.1101/2022.11.03.514906
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Lucas Schirmer
中科院分区：
文献类型：
--
作者：
Celia Lerma;Pau Badia;R. O. Ramirez Flores;Patricia Sekol;Annika Hofmann;T. Thäwel;Christian J. Riedl;F. Wünnemann;Miguel A. Ibarra;Tim Trobisch;P. Eisele;D. Schapiro;M. Haeussler;S. Hametner;J. Saez;Lucas Schirmer
多发性硬化（MS）是一种典型的中枢神经系统慢性炎症性疾病。在活动性脱髓鞘过程中初始病变形成后，炎症逐渐被划分并局限于特定的组织区域，如慢性活动性病变的病变边缘。然而，慢性组织损伤和病变扩张的细胞类型特异性和空间限制性驱动因素尚未得到很好的理解。在这里，我们通过创建ms不同炎症病变阶段的细胞类型特异性基因表达空间图谱来研究皮层下白质病变的特性。对单核和空间转录组学数据的综合分析使我们能够揭示胶质细胞、免疫细胞和基质细胞亚型多样性的模式。我们的研究结果为MS病变进展中组织微环境从“稳态”到致病或“功能失调”状态的转化提供了见解。我们期望这项研究将有助于确定空间分辨的细胞类型特异性生物标志物和未来MS介入试验的治疗靶点。
Multiple sclerosis (MS) is a prototypic chronic-inflammatory disease of the central nervous system. After initial lesion formation during active demyelination, inflammation is gradually compartmentalized and restricted to specific tissue areas such as the lesion rim in chronic-active lesions. However, the cell type-specific and spatially restricted drivers of chronic tissue damage and lesion expansion are not well understood. Here, we investigated the properties of subcortical white matter lesions by creating a cell type-specific spatial map of gene expression across various inflammatory lesion stages in MS. An integrated analysis of single-nucleus and spatial transcriptomics data enabled us to uncover patterns of glial, immune and stromal cell subtype diversity, as well as to identify cell-cell communication and signaling signatures across lesion and non-lesion tissue areas in MS. Our results provide insights into the conversion of the tissue microenvironment from a ‘homeostatic’ to a pathogenic or ‘dysfunctional’ state underlying lesion progression in MS. We expect that this study will help identify spatially resolved cell type-specific biomarkers and therapeutic targets for future interventional trials in MS.
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