Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection
Abstract
Core histones including H2A, H2B, H3, and H4 are key modulators of cellular repair, transcription, and replication within eukaryotic cells, playing vital roles within the pathogenesis of disease and cellular responses to environmental stimuli. Traditional mass spectrometry (MS) based bottom-up and top-down proteomics allows for the comprehensive identification of proteins and of post-translational modification (PTM) harboring proteoforms. However, these methodologies have difficulties preserving near cellular spatial distributions because they typically require laser capture microdissection (LCM) and advanced sample preparation techniques. Herein, we coupled matrix-assisted laser desorption/ionization (MALDI) source with a Thermo Scientific Q-Exactive HF Orbitrap MS upgraded with ultra-high mass range (UHMR) boards for the first demonstration of complementary high-resolution accurate mass measurements of proteoforms directly from tissue using this benchtop mass spectrometer. The platform achieved isotopic resolution throughout the detected mass range, providing confident assignments of proteoforms with low ppm mass error and a vastly improved duty cycle over other Fourier transform mass analyzers. Proteoform mapping of core histones was demonstrated on sections of human kidney at near-cellular spatial resolution, with several key distributions of histone and other proteoforms noted within both healthy biopsy and a section from a renal cell carcinoma (RCC) containing nephrectomy. Further, the use ofmore »
- Authors:
-
[1];
[1];
[1];
[5];
[1];
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Thermo Fisher Scientific, Bremen (Germany)
- Univ. of Texas at San Antonio, TX (United States)
- Univ. of Texas at San Antonio, TX (United States); Audie L. Murphy Memorial VA Hospital, San Antonio, TX (United States)
- Thermo Fisher Scientific, Bremen (Germany); Utrecht University (Netherlands)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
- OSTI Identifier:
- 1893833
- Report Number(s):
- PNNL-SA-170716
Journal ID: ISSN 0003-2700
- Grant/Contract Number:
- AC05-76RL01830; UG3CA256959-01
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Analytical Chemistry
- Additional Journal Information:
- Journal Volume: 94; Journal Issue: 37; Journal ID: ISSN 0003-2700
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; ions; lipids; mass spectrometry; peptides and proteins; soil acidification
Citation Formats
Zemaitis, Kevin J., Veličković, Dušan, Kew, William R., Fort, Kyle L., Reinhardt-Szyba, Maria, Pamreddy, Annapurna, Ding, Yanli, Kaushik, Dharam, Sharma, Kumar, Makarov, Alexander A., Zhou, Mowei, and Paša-Tolić, Ljiljana. Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection. United States: N. p., 2022.
Web. doi:10.1021/acs.analchem.2c01034.
Zemaitis, Kevin J., Veličković, Dušan, Kew, William R., Fort, Kyle L., Reinhardt-Szyba, Maria, Pamreddy, Annapurna, Ding, Yanli, Kaushik, Dharam, Sharma, Kumar, Makarov, Alexander A., Zhou, Mowei, & Paša-Tolić, Ljiljana. Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection. United States. https://doi.org/10.1021/acs.analchem.2c01034
Zemaitis, Kevin J., Veličković, Dušan, Kew, William R., Fort, Kyle L., Reinhardt-Szyba, Maria, Pamreddy, Annapurna, Ding, Yanli, Kaushik, Dharam, Sharma, Kumar, Makarov, Alexander A., Zhou, Mowei, and Paša-Tolić, Ljiljana. Tue .
"Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection". United States. https://doi.org/10.1021/acs.analchem.2c01034. https://www.osti.gov/servlets/purl/1893833.
@article{osti_1893833,
title = {Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection},
author = {Zemaitis, Kevin J. and Veličković, Dušan and Kew, William R. and Fort, Kyle L. and Reinhardt-Szyba, Maria and Pamreddy, Annapurna and Ding, Yanli and Kaushik, Dharam and Sharma, Kumar and Makarov, Alexander A. and Zhou, Mowei and Paša-Tolić, Ljiljana},
abstractNote = {Core histones including H2A, H2B, H3, and H4 are key modulators of cellular repair, transcription, and replication within eukaryotic cells, playing vital roles within the pathogenesis of disease and cellular responses to environmental stimuli. Traditional mass spectrometry (MS) based bottom-up and top-down proteomics allows for the comprehensive identification of proteins and of post-translational modification (PTM) harboring proteoforms. However, these methodologies have difficulties preserving near cellular spatial distributions because they typically require laser capture microdissection (LCM) and advanced sample preparation techniques. Herein, we coupled matrix-assisted laser desorption/ionization (MALDI) source with a Thermo Scientific Q-Exactive HF Orbitrap MS upgraded with ultra-high mass range (UHMR) boards for the first demonstration of complementary high-resolution accurate mass measurements of proteoforms directly from tissue using this benchtop mass spectrometer. The platform achieved isotopic resolution throughout the detected mass range, providing confident assignments of proteoforms with low ppm mass error and a vastly improved duty cycle over other Fourier transform mass analyzers. Proteoform mapping of core histones was demonstrated on sections of human kidney at near-cellular spatial resolution, with several key distributions of histone and other proteoforms noted within both healthy biopsy and a section from a renal cell carcinoma (RCC) containing nephrectomy. Further, the use of MALDI-MS imaging (MSI) for proteoform mapping demonstrates several steps towards high-throughput accurate identification of proteoforms and provides a new tool for mapping biomolecule distributions throughout tissue sections in extended mass ranges.},
doi = {10.1021/acs.analchem.2c01034},
journal = {Analytical Chemistry},
number = 37,
volume = 94,
place = {United States},
year = {Tue Sep 06 00:00:00 EDT 2022},
month = {Tue Sep 06 00:00:00 EDT 2022}
}
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