Evidence map›Paper›PMID 41723523›Full record

ArticleCell communication and signaling : CCS2026

Spatial protein expression patterns across pathologically-associated fibers revealed molecular specialization in inclusion body myositis.

T I Nijssen, S Davis, R A O'Shaughnessy, E Bos, A J van der Kooi, J Raaphorst, E Aronica, R Fischer, B M Kessler, Vered Raz

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Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

T I NijssenDepartment of Human Genetics, Leiden University Medical Center, Postbus 9600, Leiden, 2300 RC, The Netherlands.
S DavisCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
R A O'ShaughnessyDepartment of Human Genetics, Leiden University Medical Center, Postbus 9600, Leiden, 2300 RC, The Netherlands.
E BosDepartment of Chemical Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
A J van der KooiDepartment of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
J RaaphorstDepartment of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
E AronicaDepartment of Neuropathology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
R FischerCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
B M KesslerCentre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Vered RazDepartment of Human Genetics, Leiden University Medical Center, Postbus 9600, Leiden, 2300 RC, The Netherlands. v.raz@lumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesIn Inclusion Body Myositis (IBM), myofibers undergo structural and functional changes, including increased regeneration, atrophy, and fibrosis. The molecular mechanisms driving pathologically -associated fibers (PAF) remain poorly understood.

methodsWe developed a myofiber-level proteomic workflow to identify protein signatures of three PAF subtypes. Laser-capture microdissection mass spectrometry of immunolabeled cryosections was performed, complemented by immunofluorescence and electron microscopy validation.

resultsRegenerating fibers expressing embryonic myosin heavy chain showed greater molecular similarity to centrally nucleated fibers than to fibers adjacent to inflammation, which were enriched in aggregation-prone proteins. These distinct proteomic profiles revealed disruptions in protein homeostasis and proteasome composition, implicating impaired proteostasis in defective regeneration. In addition, alterations in HNRNPA1 subcellular localization across PAF subtypes suggest a potential role in driving protein aggregation and inflammation in IBM.

conclusionsThis study underscores the value of spatial proteomics for dissecting localized pathological processes in muscle disease. It highlights the molecular heterogeneity of IBM myofibers and suggests that PAF subtype-specific mechanisms underlie impaired regeneration while pointing to potential drivers of IBM pathology.

Indexed as

Muscle Fibers, SkeletalMyositis, Inclusion BodyAnimalsHumansProteomicsRegenerationHistopathologyInclusion body myositisPathogenesis-associated myofibersRegenerative myofibersSpatial proteomics

Identifiers

PMID41723523
PMCPMC13032386

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.