Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry

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 ident...

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Bibliographic Details
Published in:Frontiers in physiology Vol. 13; p. 837773
Main Authors: Kruse, Angela R. S., Spraggins, Jeffrey M.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 11.02.2022
Subjects:
kidney
lipidomics
mass spectrometry
metabolomics
multimodal imaging
Physiology
proteomics
kidney
proteomics
metabolomics
mass spectrometry
HuBMAP
KPMP
multimodal imaging
lipidomics
ISSN:1664-042X, 1664-042X
Online Access:Get full text
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Summary: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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Edited by: Bruce Molitoris, Indiana University, United States
Reviewed by: Christoph Kuppe, RWTH Aachen University, Germany
This article was submitted to Renal and Epithelial Physiology, a section of the journal Frontiers in Physiology
ISSN:1664-042X
1664-042X
DOI:10.3389/fphys.2022.837773