PXD066920-1

PXD066920 is an original dataset announced via ProteomeXchange.

Title	Pathological extracellular matrix changes in decellularized normal appearing grey matter and subpial grey matter multiple sclerosis lesions
Description	Multiple sclerosis (MS) is chronic disease of the central nervous system characterized by demyelinated lesions in both grey and white matter. While white matter lesions are typically associated with inflammatory demyelination, grey matter lesions (GML) often indicate ongoing neurodegenerative processes. GML are linked to clinical disability, though non-demyelinated areas in grey matter also exhibit underlying neuropathology. In grey matter, the extracellular matrix (ECM) plays a vital role in maintaining neuronal health, with perineuronal nets (PNNs) functioning as barriers, regulating synaptic stability and limiting postsynaptic receptor mobility. Microglia impact ECM composition by secreting ECM-degrading matrix metalloproteinases (MMPs), while the ECM, in turn, affects microglia behaviour. In this study, we examined differences in non-cell-associated ECM composition between human control and MS tissue and investigate how this ECM influences microglia. Label-free quantitative mass spectrometry of decellularized control grey matter (dCGM) and normal appearing grey matter (dNAGM) tissue slices revealed differentially abundant ECM proteins, and several ECM proteins uniquely present in either dNAGM or dCGM. The altered ECM composition of dNAGM involved changes in PNN, synaptic and basement membrane components, potentially impacting synaptic and blood-brain barrier function. The ECM composition of decellularized GML (dGML) and surrounding perilesional grey matter (dPLGM) appeared relatively similar. When decellularized human grey matter brain tissue was recellularized with primary microglia, half of the microglia population lost IBA1 expression on dNAGM and dGML, while a portion of the remaining IBA1+ microglia expressed the proinflammatory marker iNOS . These findings suggest changes in non-cell-associated ECM composition in the absence of demyelination, potentially influencing microglial behaviour and contributing to MS pathology.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-23_01:46:36.099.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justina Clarinda Wolters
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-04 03:40:55	ID requested
⏵ 1	2026-03-23 01:46:36	announced

Dataset with its publication pending

submitter keyword: ECM, rat,multiple sclerosis, human, GML, mouse

Dr JC Wolters
contact affiliation	Laboratory of Pediatrics, UMCG, The Netherlands
contact email	j.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliation	UMCG
contact email	j.c.wolters@umcg.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066920
     1. Label: PRIDE project
     2. Name: Pathological extracellular matrix changes in decellularized normal appearing grey matter and subpial grey matter multiple sclerosis lesions