Imaging Mass Spectrometry Reveals Alterations in N-Linked Glycosylation That Are Associated With Histopathological Changes in Nonalcoholic Steatohepatitis in Mouse and Human

Ochoa-Rios, Shaaron; O'Connor, Ian P; Kent, Lindsey N.; Clouse, Julian M.; Hadjiyannis, Yannis; Koivisto, Christopher S.; Pécot, Thierry; Angel, Peggi; Drake, Richard; Leone, Gustavo; Mehta, Anand; Rockey, Don C.

doi:10.1016/j.mcpro.2022.100225

Cited by 10 publications

(9 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To characterize the N-linked glycan profile in liver disease progression, we used MALDI-IMS. − , MALDI-IMS allows for qualitative analysis of N-linked glycan structures in situ. We were first interested in the full-tissue N-glycome characterization of MASL/MASH progression based on the type of N-glycans that was identified in all groups.…”

Section: Resultsmentioning

confidence: 99%

“…This N-glycan structure attachment occurs at the Asparagine (Asn) residue of the glycoproteins primarily within a consensus sequence of N-X-S/T, where X can be any amino acid except proline . While N-linked glycosylation is involved in many biological roles, such as protein folding, cell signaling, and immune response, it is also used in the clinic as a biomarker for liver cancers: AFP-L3 for HCC and CA19-9 for CCA. ,, N-Linked glycan alterations have been widely studied in different liver diseases, including cirrhosis, HCC, fatty liver, and NASH. − Indeed, we have shown that HCC is associated with increased levels of branched and fucosylated N-glycan , and liver fibrosis. ,− It is important to understand these alterations with time in the context of a liver disease progression because it is known that N-glycosylation can impact cell signaling and downstream signaling pathways, leading to increased cell proliferation. ,− Knowing if these N-glycan modifications come before or after pathological alterations will help identify the roles they play in disease progression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spatial Omics Reveals that Cancer-Associated Glycan Changes Occur Early in Liver Disease Development in a Western Diet Mouse Model of MASLD

Ochoa-Rios,

Grauzam,

Gregory

et al. 2024

J. Proteome Res.

Self Cite

View full text Add to dashboard Cite

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disease and comprises different stages of liver damage; it is significantly associated with obese and overweight patients. Untreated MASLD can progress to lifethreatening end-stage conditions, such as cirrhosis and liver cancer. N-Linked glycosylation is one of the most common posttranslational modifications in the cell surface and secreted proteins. N-Linked glycan alterations have been established to be signatures of liver diseases. However, the N-linked glycan changes during the progression of MASLD to liver cancer are still unknown. Here, we induced different stages of MASLD in mice and liver-cancer-related phenotypes and elucidated the N-glycome profile during the progression of MASLD by quantitative and qualitative profiling in situ using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). Importantly, we identified specific N-glycan structures including fucosylated and highly branched N-linked glycans at very early stages of liver injury (steatosis), which in humans are associated with cancer development, establishing the importance of these modifications with disease progression. Finally, we report that N-linked glycan alterations can be observed in our models by MALDI-IMS before liver injury is identified by histological analysis. Overall, we propose these findings as promising biomarkers for the early diagnosis of liver injury in MASLD.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spatial Omics Reveals that Cancer-Associated Glycan Changes Occur Early in Liver Disease Development in a Western Diet Mouse Model of MASLD

Ochoa-Rios,

Grauzam,

Gregory

et al. 2024

J. Proteome Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Here, the authors suggested that during early stages of liver disease, significant changes in the core fucosylation might drive liver damage progression to NASH. [143] The spatial single-nuclear metabolomics method was the first to allow the segmentation and analysis of a single nuclear metabolic profile directly on tissue sections. This new multiscale spatial resolution platform combines experiments and computational algorithms to quantitatively characterize the metabolic intracellular or intercellular features.…”

Section: Ldi-msimentioning

confidence: 99%

“…• N-glycosylation modifications correlated with fibrosis score and liver histology changes 2022 Ochoa-rios et al [143] Liver tissue from mice under fasting conditions, ND, and HFD…”

Section: Maldi-msimentioning

confidence: 99%

Spatial metabolomics and its application in the liver

et al. 2023

View full text Add to dashboard Cite

Hepatocytes work in highly structured, repetitive hepatic lobules. Blood flow across the radial axis of the lobule generates oxygen, nutrient, and hormone gradients, which result in zoned spatial variability and functional diversity. This large heterogeneity suggests that hepatocytes in different lobule zones may have distinct gene expression profiles, metabolic features, regenerative capacity, and susceptibility to damage. Here, we describe the principles of liver zonation, introduce metabolomic approaches to study the spatial heterogeneity of the liver, and highlight the possibility of exploring the spatial metabolic profile, leading to a deeper understanding of the tissue metabolic organization. Spatial metabolomics can also reveal intercellular heterogeneity and its contribution to liver disease. These approaches facilitate the global characterization of liver metabolic function with high spatial resolution along physiological and pathological time scales. This review summarizes the state of the art for spatially resolved metabolomic analysis and the challenges that hinder the achievement of metabolome coverage at the single-cell level. We also discuss several major contributions to the understanding of liver spatial

show abstract

“…An alternative approach for in situ analysis, matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI), has emerged, which allows the determination of the spatial distribution of endogenous metabolites, peptides, or proteins [33,34]. In recent MSI-based studies focusing on N-glycosylation, thin tissue slices were washed and incubated with de-N-glycanase (PNGase F) to release the N-linked glycans prior to MALDI analysis [35][36][37][38]. This MALDI MSI strategy revealed marked nuance in changes in N-glycans within benign tissues versus regions of tumors [9,[39][40][41][42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 99%

In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry

Escobar

Seeley

Serrano-Negrón

et al. 2023

Cancers

View full text Add to dashboard Cite

Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. We use this strategy to monitor O-GlcNAc within hepatic VX2 tumor tissue. We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression.

show abstract

Imaging Mass Spectrometry Reveals Alterations in N-Linked Glycosylation That Are Associated With Histopathological Changes in Nonalcoholic Steatohepatitis in Mouse and Human

Cited by 10 publications

References 59 publications

Spatial Omics Reveals that Cancer-Associated Glycan Changes Occur Early in Liver Disease Development in a Western Diet Mouse Model of MASLD

Spatial Omics Reveals that Cancer-Associated Glycan Changes Occur Early in Liver Disease Development in a Western Diet Mouse Model of MASLD

Spatial metabolomics and its application in the liver

In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry

Contact Info

Product

Resources

About