Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Glycogen In Situ

Hawkinson, Tara R.; Sun, Runyuan

doi:10.1007/978-1-0716-2030-4_15

Cited by 9 publications

(10 citation statements)

References 38 publications

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“…Oligomerization of simple sugars to glycogen results in increased polarity and decreased solubility; therefore, quantitative, and spatial analyses of complex carbohydrates has been challenging. To address this limitation, a new technique was recently developed employing enzyme-assisted matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) that can simultaneously perform spatial profiling of both glycogen and N-linked glycans from formalin-fixed paraffin-embedded (FFPE) mammalian tissue sections in situ, preserving important anatomical regions 15 , 22 .…”

Section: Introductionmentioning

confidence: 99%

“…The end result is a multidimensional, information-rich dataset containing metabolic features from normal and diseased tissues 24 , 30 – 32 . Recent advances in MALDI-MSI enable the detection of complex carbohydrates such as proteoglycans 33 , N-linked glycans 34 , and glycogen architecture 15 , 22 from FFPE tissue sections. The ability to utilize FFPE tissue sections dramatically increases the accessibility to banked clinical specimens with up to decades of patient-matched metadata.…”

Section: Introductionmentioning

confidence: 99%

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Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

et al. 2023

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Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

et al. 2023

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“…The development of GCMS‐based methods to detect glycogen dramatically improved accuracy and sensitivity (Andres et al, 2020; Young et al, 2020). MALDI–MSI combines the accuracy and sensitivity of mass spectrometry with added spatial information and glycogen architecture (Conroy et al, 2023; Hawkinson & Sun, 2022; Young et al, 2022). This technique offers crucial quantification of regional and architectural information and is approaching single‐cell resolution.…”

Section: Brain Glycogen – Detection and Localizationmentioning

confidence: 99%

The multifaceted roles of the brain glycogen

Markussen

Corti

Byrne

et al. 2023

Journal of Neurochemistry

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Glycogen is a biologically essential macromolecule that is directly involved in multiple human diseases. While its primary role in carbohydrate storage and energy metabolism in the liver and muscle is well characterized, recent research has highlighted critical metabolic and non‐metabolic roles for glycogen in the brain. In this review, the emerging roles of glycogen homeostasis in the healthy and diseased brain are discussed with a focus on advancing our understanding of the role of glycogen in the brain. Innovative technologies that have led to novel insights into glycogen functions are detailed. Key insights into how cellular localization impacts neuronal and glial function are discussed. Perturbed glycogen functions are observed in multiple disorders of the brain, including where it serves as a disease driver in the emerging category of neurological glycogen storage diseases (n‐GSDs). n‐GSDs include Lafora disease (LD), adult polyglucosan body disease (APBD), Cori disease, Glucose transporter type 1 deficiency syndrome (G1D), GSD0b, and late‐onset Pompe disease (PD). They are neurogenetic disorders characterized by aberrant glycogen which results in devastating neurological and systemic symptoms. In the most severe cases, rapid neurodegeneration coupled with dementia results in death soon after diagnosis. Finally, we discuss current treatment strategies that are currently being developed and have the potential to be of great benefit to patients with n‐GSD. Taken together, novel technologies and biological insights have resulted in a renaissance in brain glycogen that dramatically advanced our understanding of both biology and disease. Future studies are needed to expand our understanding and the multifaceted roles of glycogen and effectively apply these insights to human disease.image

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“…High spatial resolution MS imaging is beginning to show some promise beyond protein analysis, including with stable isotope tracers (Wang et al, 2022). MS imaging using MALDI -FT MS is especially well suited analyzing for surface protein glycosylation, with spatial resolution determined by the laser spot size which is typically in the range 10-50 m, close to individual cellular resolution (Hawkinson and Sun, 2022;Powers et al, 2014) Using longer wavelength lasers (in the near IR), more labile sugars such as sialic acid were preserved in paraffin embedded blocks (Pace et al, 2022). As indicated in Fig.…”

Section: Mass Spectrometry-based Metabolic Imagingmentioning

confidence: 99%

Single cell metabolism: current and future trends

et al. 2022

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Single cell metabolomics is an emerging and rapidly developing field that complements developments in single cell analysis by genomics and proteomics. Major goals include mapping and quantifying the metabolome in sufficient detail to provide useful information about cellular function in highly heterogeneous systems such as tissue, ultimately with spatial resolution at the individual cell level. The chemical diversity and dynamic range of metabolites poses particular challenges for detection, identification and quantification. In this review we discuss both significant technical issues of measurement and interpretation, and progress toward addressing them, with recent examples from diverse biological systems. We provide a framework for further directions aimed at improving workflow and robustness so that such analyses may become commonly applied, especially in combination with metabolic imaging and single cell transcriptomics and proteomics.

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Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Glycogen In Situ

Cited by 9 publications

References 38 publications

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

The multifaceted roles of the brain glycogen

Single cell metabolism: current and future trends

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