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PXD050768

PXD050768 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleExtracellular vesicles derived from MPSIII microglia cell model impair neurite growth
DescriptionMicroglia is emerging as a key player in the progression of neurodegenerative diseases. In pediatric neurodegenerative diseases like mucopolysaccharidosis type III (MPSIII), the progressive accumulation of abnormal glycosaminoglycans (GAGs) induces a severe neuroinflammation by triggering a microglial production of pro-inflammatory cytokines and chemokines via TLR4-dependent pathway.We have already shown the essential role of microglia in the development of neuroinflammation but the extent of its contribution in the neuropathology of MPSIII still remains unclear. Microglia interacts with other cells in the CNS via several mechanisms, including extracellular vesicle (EV) release. Although EVs have been shown to be implicated in the pathogenesis of adult neurodegenerative diseases, no reports have addressed the proteins and small RNAs profile of EVs released by microglia in the context of MPS and the effect of these EVs on neuronal functions. Here, we isolated EVs sub-populations from conditioned media of the murine BV-2 microglial cell line treated with GAG purified from urines of MPSIII patients and from age-matched unaffected children. By label-free quantitative proteomic using LC-MS/MS, we showed that MPS III-EVs are enriched in proteins involved in the inflammatory response and more specifically in neuroinflammation. On the other hand, proteins involved in axonal guidance, myelination or synaptogenesis were less abundant in MPSIII-EVs. RNA sequencing analysis revealed that MPSIII-EVs are highly enriched in 4 miRNAs - miR-155-5p, miR-146a-5p, miR-221-3p and miR-100-5p, also involved in neuroinflammation and neurodevelopment pathways. Moreover, we showed by immunofluorescence on primary cortical neurons isolated from wild type pups that MPSIII microglia-EVs reduce neurites total area, impair dendritic arborization, with a higher number of immature dendritic spines and also cause an increase in soma swelling, thus inducing a phenotype close to that observed in MPSIII brain mice. Theses findings uncover that MPSIII microglia-EVs can deliver a specific molecular message to surrounding naive cells and thus propagate neuroinflammation and deprive neurons of neurodevelopmental molecules.This work is the first report on the content of EVs released by MPSIII microglia and reveals a disease-associated signature, providing a framework for future studies on biomarkers to evaluate efficiency of emerging therapies.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_13:29:07.894.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChiara guerrera
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro 2
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-19 08:23:26ID requested
12025-05-06 13:29:08announced
Publication List
10.1186/s10020-024-00953-1;
Dias C, Ballout N, Morla G, Alileche K, Santiago C, Guerrera IC, Chaubet A, Ausseil J, Trudel S, Extracellular vesicles from microglial cells activated by abnormal heparan sulfate oligosaccharides from Sanfilippo patients impair neuronal dendritic arborization. Mol Med, 30(1):197(2024) [pubmed]
Keyword List
submitter keyword: GAG,EVs, microglia cells, MPSIII, Mouse, timsTOF Pro2, LC-MS/MS
Contact List
Ida Chiara Guerrera
contact affiliationChiara Guerrera, IRHC, HDR Head of the Necker Proteomics Faculty of Medecine, University Paris Cité SFR Necker INSERM US24 160 rue de Vaugirard | 75015 Paris Tél. 01 40 61 54 6
contact emailchiara.guerrera@inserm.fr
lab head
Chiara guerrera
contact affiliationNecker proteomics, INSERM
contact emailchiara.guerrera@inserm.fr
dataset submitter
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