Proteoform-Selective Imaging of Tissues Using Mass Spectrometry**

Manxi Yang; Hang Hu; Pei Su; Paul M. Thomas; Jeannie M. Camarillo; Joseph B. Greer; Bryan P. Early; Ryan T. Fellers; Neil L. Kelleher; Julia Laskin

doi:10.1002/anie.202200721

Proteoform-Selective Imaging of Tissues Using Mass Spectrometry**

Manxi Yang, Hang Hu, Pei Su, Paul M. Thomas, Jeannie M. Camarillo, Joseph B. Greer, Bryan P. Early, Ryan T. Fellers, Neil L. Kelleher^*, Julia Laskin^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform-specific analysis of the proteome. Herein, we employ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) for the proteoform-selective imaging of biological tissues. Nano-DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS) directly on the tissue. Proof-of-concept experiments demonstrate that nano-DESI MSI combined with on-tissue top-down proteomics is ideally suited for the proteoform-selective imaging of tissue sections. Using rat brain tissue as a model system, we provide the first evidence of differential proteoform expression in different regions of the brain.

Original language	English (US)
Article number	e202200721
Journal	Angewandte Chemie - International Edition
Volume	61
Issue number	29
DOIs	https://doi.org/10.1002/anie.202200721
State	Published - Jul 18 2022

Funding

The authors gratefully acknowledge the financial support from the National Institutes of Health (NIH) Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under awards UG3HL145593 and UH3CA255132 (HuBMAP Program, J.L.), UH3CA246635 (HuBMAP Program, N.L.K.), and P41GM108569 (N.L.K.), and the support from National Science Foundation (NSF) under awards #1916691 (Center for Bioanalytic Metrology, J.L.). MSI data analysis tools used in this study were developed with support from NSF-1808136 and NSF-2108729 (J.L.). We thank Drs. Elizabeth K. Neumann and Jeffrey M. Spraggins (Vanderbilt University) for providing rat brain tissue sections. The authors gratefully acknowledge the financial support from the National Institutes of Health (NIH) Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under awards UG3HL145593 and UH3CA255132 (HuBMAP Program, J.L.), UH3CA246635 (HuBMAP Program, N.L.K.), and P41GM108569 (N.L.K.), and the support from National Science Foundation (NSF) under awards #1916691 (Center for Bioanalytic Metrology, J.L.). MSI data analysis tools used in this study were developed with support from NSF‐1808136 and NSF‐2108729 (J.L.). We thank Drs. Elizabeth K. Neumann and Jeffrey M. Spraggins (Vanderbilt University) for providing rat brain tissue sections.

Keywords

Mass Spectrometry Imaging
On-Tissue Top-down Proteomics
Post-Translational Modifications
Proteoforms

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.202200721

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abstract = "Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform-specific analysis of the proteome. Herein, we employ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) for the proteoform-selective imaging of biological tissues. Nano-DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS) directly on the tissue. Proof-of-concept experiments demonstrate that nano-DESI MSI combined with on-tissue top-down proteomics is ideally suited for the proteoform-selective imaging of tissue sections. Using rat brain tissue as a model system, we provide the first evidence of differential proteoform expression in different regions of the brain.",

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AU - Fellers, Ryan T.

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AU - Laskin, Julia

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KW - Post-Translational Modifications

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Proteoform-Selective Imaging of Tissues Using Mass Spectrometry**

Abstract

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Keywords

ASJC Scopus subject areas

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