Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection

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

doi:10.1021/acs.analchem.2c01034

Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection

Journal Article · Tue Sep 06 00:00:00 EDT 2022 · Analytical Chemistry

DOI:https://doi.org/10.1021/acs.analchem.2c01034· OSTI ID:1893833

^[1]; ^[1]; ^[1]; Fort, Kyle L. ^[2]; Reinhardt-Szyba, Maria ^[2]; Pamreddy, Annapurna ^[3]; Ding, Yanli ^[3]; Kaushik, Dharam ^[3]; Sharma, Kumar ^[4]; ^[5]; ^[1]; Paša-Tolić, Ljiljana ^[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)

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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1893833

Report Number(s):: PNNL-SA-170716

Journal Information:: Analytical Chemistry, Journal Name: Analytical Chemistry Journal Issue: 37 Vol. 94; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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