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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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Autores principales: Kruse, Angela R. S., Spraggins, Jeffrey M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874197/
https://www.ncbi.nlm.nih.gov/pubmed/35222094
http://dx.doi.org/10.3389/fphys.2022.837773
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author Kruse, Angela R. S.
Spraggins, Jeffrey M.
author_facet Kruse, Angela R. S.
Spraggins, Jeffrey M.
author_sort Kruse, Angela R. S.
collection PubMed
description 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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spelling pubmed-88741972022-02-26 Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry Kruse, Angela R. S. Spraggins, Jeffrey M. Front Physiol Physiology 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. Frontiers Media S.A. 2022-02-11 /pmc/articles/PMC8874197/ /pubmed/35222094 http://dx.doi.org/10.3389/fphys.2022.837773 Text en Copyright © 2022 Kruse and Spraggins. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Kruse, Angela R. S.
Spraggins, Jeffrey M.
Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry
title Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry
title_full Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry
title_fullStr Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry
title_full_unstemmed Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry
title_short Uncovering Molecular Heterogeneity in the Kidney With Spatially Targeted Mass Spectrometry
title_sort uncovering molecular heterogeneity in the kidney with spatially targeted mass spectrometry
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874197/
https://www.ncbi.nlm.nih.gov/pubmed/35222094
http://dx.doi.org/10.3389/fphys.2022.837773
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