In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues.
Ewing sarcoma
MALDI imaging
glycogen
glycogen storage disease
spatial metabolism
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
08 11 2022
08 11 2022
Historique:
revised:
25
07
2022
received:
22
03
2022
accepted:
03
08
2022
pubmed:
6
9
2022
medline:
10
11
2022
entrez:
5
9
2022
Statut:
ppublish
Résumé
Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.
Identifiants
pubmed: 36059248
doi: 10.15252/emmm.202216029
pmc: PMC9641418
doi:
Substances chimiques
Glycogen
9005-79-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16029Subventions
Organisme : NCI NIH HHS
ID : R01 CA266004
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA165990
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS116824
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA177558
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA264165
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS097197
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG066653
Pays : United States
Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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