Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution
Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution
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DOI：
10.1038/s41467-019-13858-z
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发表时间：
2020-01-07
影响因子：
16.6
通讯作者：
Burnum-Johnson, Kristin E.
中科院分区：
文献类型：
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作者：
Piehowski, Paul D.;Zhu, Ying;Burnum-Johnson, Kristin E.
生物组织表现出复杂的空间异质性，指导着多细胞生物体的功能。蛋白质表达的量化对于阐明复杂生物组装的过程是必不可少的。成像质谱学(IMS)是一种用于绘制组织表面代谢物和脂类的空间分布的强大工具，但技术挑战限制了IMS在蛋白质组分析中的应用。探测蛋白质组空间分布的方法通常依赖于标记和/或抗体的使用，这限制了多路传输，并且需要对蛋白质靶标的先验知识。过去跨组织进行空间分辨蛋白质组测量的努力一直有限，空间分辨率和蛋白质组覆盖范围有限，一直依赖人工工作流程。在这里，我们展示了一种自动化的成像方法，利用无标记纳米蛋白质组学来分析组织体素，在准备胚泡植入的小鼠子宫组织切片上以100微米的空间分辨率生成>；2000蛋白质的特定细胞类型的定量图像。
Biological tissues exhibit complex spatial heterogeneity that directs the functions of multicellular organisms. Quantifying protein expression is essential for elucidating processes within complex biological assemblies. Imaging mass spectrometry (IMS) is a powerful emerging tool for mapping the spatial distribution of metabolites and lipids across tissue surfaces, but technical challenges have limited the application of IMS to the analysis of proteomes. Methods for probing the spatial distribution of the proteome have generally relied on the use of labels and/or antibodies, which limits multiplexing and requires a priori knowledge of protein targets. Past efforts to make spatially resolved proteome measurements across tissues have had limited spatial resolution and proteome coverage and have relied on manual workflows. Here, we demonstrate an automated approach to imaging that utilizes label-free nanoproteomics to analyze tissue voxels, generating quantitative cell-type-specific images for >2000 proteins with 100-mu m spatial resolution across mouse uterine tissue sections preparing for blastocyst implantation.