Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry.

Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry.
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DOI:
10.3389/fphys.2022.837773
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发表时间:
2022
影响因子:
4
通讯作者:
Spraggins JM
Spraggins JM
中科院分区:
医学2区
文献类型:
--
作者:
Kruse ARS;Spraggins JM

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肾脏通过在三维空间中协调大约一百万个多功能肾单位来发挥功能。对肾脏的分子理解依赖于肾匀浆的转录组学、蛋白质组学和代谢组学分析,但这些方法不能解决细胞身份和空间背景。分离细胞的质谱分析保留了细胞身份,但没有关于其细胞邻域和细胞外基质的信息。空间靶向质谱法是唯一适合于分子表征肾组织,同时保留原位细胞背景。本文综述了肾脏组织空间靶向质谱分析的方法学和技术进展。分析技术如激光捕获显微切割(LCM)结合液相色谱串联质谱法提供特定组织区域的深度分子覆盖,而成像技术如基质辅助激光解吸/电离成像质谱法(MALDI IMS)以更高的空间分辨率对规则间隔的组织区域进行分子分析。这些技术各自促进了我们对肾单位区域(如肾小球和近端小管)异质性的理解,预计它们的组合将深刻扩展我们对健康和疾病中肾脏的了解。
The kidney functions through the coordination of approximately one million multifunctional nephrons in 3-dimensional space. Molecular understanding of the kidney has relied on transcriptomic, proteomic, and metabolomic analyses of kidney homogenate, but these approaches do not resolve cellular identity and spatial context. Mass spectrometry analysis of isolated cells retains cellular identity but not information regarding its cellular neighborhood and extracellular matrix. Spatially targeted mass spectrometry is uniquely suited to molecularly characterize kidney tissue while retaining in situ cellular context. This review summarizes advances in methodology and technology for spatially targeted mass spectrometry analysis of kidney tissue. Profiling technologies such as laser capture microdissection (LCM) coupled to liquid chromatography tandem mass spectrometry provide deep molecular coverage of specific tissue regions, while imaging technologies such as matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) molecularly profile regularly spaced tissue regions with greater spatial resolution. These technologies individually have furthered our understanding of heterogeneity in nephron regions such as glomeruli and proximal tubules, and their combination is expected to profoundly expand our knowledge of the kidney in health and disease.
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