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Highly multiplexed molecular and cellular mapping of breast cancer tissue in three dimensions using mass tomography.
bioRxiv - Cell Biology Pub Date : 2020-05-26 , DOI: 10.1101/2020.05.24.113571
Raúl Catena , Alaz Özcan , Laura Kütt , Alex Plüss , Peter Schraml , Holger Moch , Bernd Bodenmiller ,

A holistic understanding of tissue and organ structures and their functions requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) makes possible the detection of up to 40 antigens and specific nucleic acids simultaneously using metal-tagged antibodies or nucleic acid probes, respectively, but has so far been restricted to two-dimensional imaging. To enable use of IMC for 3D tissue analyses, we developed mass tomography, which combines quasi deformation-free serial sectioning with novel computational methods. We utilized mass tomography to analyze a breast cancer sample. The resulting 3D representation reveals spatial and cellular heterogeneity, preferential cell-to-cell interactions, detailed tissue-architecture motifs, and the unique microenvironment of a micro-invasion, where micro-metastases clonality is examined, showing that cells arising from the same invasive area, displaying very distinct phenotypes, are all able to produce initial invasive lesions. Mass tomography will provide invaluable insights into the tissue microenvironment, cellular neighborhoods, and tissue organization.

中文翻译:

使用质谱层析成像技术在三个维度上对乳腺癌组织进行高度复用的分子和细胞作图。

要全面了解组织和器官的结构及其功能,需要检测其原始三维(3D)上下文中的分子成分。成像质量细胞术(IMC)使得分别使用金属标记的抗体或核酸探针同时检测多达40种抗原和特定核酸成为可能,但是到目前为止,它仅限于二维成像。为了使IMC能够用于3D组织分析,我们开发了质量层析成像技术,该技术将准无变形串行切片与新颖的计算方法相结合。我们利用体层摄影术分析了乳腺癌样本。产生的3D图像揭示了空间和细胞异质性,优先的细胞间相互作用,详细的组织结构图案以及微侵袭的独特微环境,在这里检查了微转移的克隆性,表明来自相同浸润区域的细胞,表现出非常不同的表型,都能够产生初始浸润性病变。质谱层析成像将提供有关组织微环境,细胞邻域和组织组织的宝贵见解。
更新日期:2020-05-26
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