Spatial Metabolomics of the Human Kidney using MALDI Trapped Ion Mobility Imaging Mass Spectrometry
Spatial Metabolomics of the Human Kidney using MALDI Trapped Ion Mobility Imaging Mass Spectrometry
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DOI：
10.1021/acs.analchem.0c02051
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发表时间：
2020-10-06
影响因子：
7.4
通讯作者：
Spraggins, Jeffrey M.
中科院分区：
文献类型：
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作者：
Neumann, Elizabeth K.;Migas, Lukasz G.;Spraggins, Jeffrey M.
低分子量代谢物对于确定细胞的分子表型是必不可少的。然而，空间代谢组学工具往往缺乏灵敏度，具体和空间分辨率，以提供全面的描述，这些物种在组织中。低分子量离子的MALDI成像质谱法（IMS）特别具有挑战性，因为MALDI基质簇通常与多种代谢物离子名义上是同量异位的，需要高分辨率仪器或衍生化来规避这个问题。另一种方法是在离子检测之前进行离子迁移率分离，从而能够在不受基质离子干扰的情况下可视化代谢物。围绕低重量代谢物可视化的其他困难包括高分辨率成像，同时保持足够的离子数用于组织化学补体的广泛和代表性分析。在这里，我们使用MALDI timsTOF IMS图像低分子量代谢物在更高的空间分辨率比大多数代谢物MALDI IMS实验（20 μ m），同时保持广泛的覆盖范围内的人肾。我们证明，捕获离子迁移谱（TIMS）可以解决基质峰代谢物信号和分离同量异位素和异构体代谢物在肾脏内的不同分布。增加的离子迁移率数据维度显著增加了空间代谢组学实验的峰值容量。通过这种提高的灵敏度，我们已经在人肾组织中发现了>40种低分子量代谢物，例如分别定位于皮质、髓质和肾盂的烟酸、乙酰肉毒碱和胆碱。未来的工作将涉及进一步探索人类肾脏的代谢谱作为年龄，性别和种族的函数。
Low molecular weight metabolites are essential for defining the molecular phenotypes of cells. However, spatial metabolomics tools often lack the sensitivity, specify, and spatial resolution to provide comprehensive descriptions of these species in tissue. MALDI imaging mass spectrometry (IMS) of low molecular weight ions is particularly challenging as MALDI matrix clusters are often nominally isobaric with multiple metabolite ions, requiring high resolving power instrumentation or derivatization to circumvent this issue. An alternative to this is to perform ion mobility separation before ion detection, enabling the visualization of metabolites without the interference of matrix ions. Additional difficulties surrounding low weight metabolite visualization include high resolution imaging, while maintaining sufficient ion numbers for broad and representative analysis of the tissue chemical complement. Here, we use MALDI timsTOF IMS to image low molecular weight metabolites at higher spatial resolution than most metabolite MALDI IMS experiments (20 mu m) while maintaining broad coverage within the human kidney. We demonstrate that trapped ion mobility spectrometry (TIMS) can resolve matrix peaks from metabolite signal and separate both isobaric and isomeric metabolites with different distributions within the kidney. The added ion mobility data dimension dramatically increased the peak capacity for spatial metabolomics experiments. Through this improved sensitivity, we have found >40 low molecular weight metabolites in human kidney tissue, such as argininic acid, acetylcarnitine, and choline that localize to the cortex, medulla, and renal pelvis, respectively. Future work will involve further exploring metabolomic profiles of human kidneys as a function of age, sex, and race.