Abstract
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.
Highlights
The kidney is a complex and vital organ that filters waste products from the blood, stabilizes electrolyte and water content, and secretes essential hormones (Tryggvason and Wartiovaara, 2005; Ferraro and Fuster, 2021)
Spatially targeted mass spectrometry (MS) technologies have emerged that provide a deeper understanding of the role localized cell types, cellular neighborhoods, and functional tissue unit (FTU) play in underlying pathomechanisms (Autengruber et al, 2012; Ryan et al, 2019)
Targeted MS technologies are characterized as either profiling experiments, where a single spectral signature is collected from a discrete cell type or FTU, or as imaging experiments where MS data are collected from an array of measurement locations to visualize molecular distributions in situ (Figure 1)
Summary
The kidney is a complex and vital organ that filters waste products from the blood, stabilizes electrolyte and water content, and secretes essential hormones (Tryggvason and Wartiovaara, 2005; Ferraro and Fuster, 2021). Spatially targeted mass spectrometry (MS) technologies have emerged that provide a deeper understanding of the role localized cell types, cellular neighborhoods, and FTUs play in underlying pathomechanisms (Autengruber et al, 2012; Ryan et al, 2019). Each of these MS technologies has unique benefits and drawbacks for the study of human organs. This review highlights the application and potential of spatially targeted MS to illuminate the underlying molecular drivers of kidney health and disease
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