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Purinergic exposure induces epigenomic and transcriptomic-mediated preconditioning resembling epilepsy-associated microglial states

2024-08-16Research article Open access
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datacite.subject.fosCiências Médicas::Medicina Básica
dc.contributor.authorMartins-Ferreira, Ricardo
dc.contributor.authorCalafell-Segura, Josep
dc.contributor.authorChaves, João
dc.contributor.authorCiudad, Laura
dc.contributor.authorMartins da Silva, António
dc.contributor.authorPinho E Costa, Paulo
dc.contributor.authorLeal, Bárbara
dc.contributor.authorBallestar, Esteban
dc.date.accessioned2025-04-03T14:12:24Z
dc.date.available2025-04-03T14:12:24Z
dc.date.issued2024-08-16
dc.description.abstractMicroglia play a crucial role in a range of neuropathologies through exacerbated activation. Microglial inflammatory responses can be influenced by prior exposures to noxious stimuli, like increased levels of extracellular adenosine and ATP. These are characteristic of brain insults like epileptic seizures and could potentially shape subsequent responses through epigenetic regulation. We investigated DNA methylation and expression changes in human microglia-like cells differentiated from monocytes following ATP-mediated preconditioning. We demonstrate that microglia-like cells display homeostatic microglial features, shown by surface markers, transcriptome, and DNA methylome. After exposure to ATP, TLR-mediated activation leads to an exacerbated pro-inflammatory response. These changes are accompanied by methylation and transcriptional reprogramming associated with enhanced immune-related functions. The reprogramming associated with ATP-mediated preconditioning leads to profiles found in microglial subsets linked to epilepsy. Purine-driven microglia immune preconditioning drives epigenetic and transcriptional changes that could contribute to altered functions of microglia during seizure development and progression.por
dc.description.abstractHighlights: - Microglia-like cells replicate microglial transcriptome and DNA methylome; - Purinergic preconditioning promotes enhanced pro-inflammatory response; - Methylation and transcription of inflammatory genes are altered by ATP pre-exposure; - ATP-related expression changes mimic microglial population expanded in epilepsy.por
dc.description.sponsorshipE.B. is funded by the Spanish Ministry of Science and Innovation (MICINN) [PID2020117212RB-I00; AEI/10.13039/501100011033]. R.M-F. is funded by an FCT (Fundação para a Ciência e Tecnologia) fellowship (SFRH/BD/137900/2018). UMIB is funded by FCT Portugal (UIDB/00215/2020 and UIDP/00215/2020), and ITR (LA/P/006/2020).
dc.identifier.citationiScience. 2024 Jul 20;27(8):110546. doi: 10.1016/j.isci.2024.110546. eCollection 2024 Aug 16
dc.identifier.doi10.1016/j.isci.2024.110546
dc.identifier.issn2589-0042
dc.identifier.pmid39184445
dc.identifier.urihttp://hdl.handle.net/10400.18/10471
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationEpigenetic regulation of signalling pathways in MTLE-HS and its impact on epileptogenesis
dc.relationUnit for Multidisciplinary Research in Biomedicine
dc.relationUnit for Multidisciplinary Research in Biomedicine
dc.relationLaboratory for Integrative and Translational Research in Population Health
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S2589004224017711?via%3Dihub
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectEpigenetics
dc.subjectEpilepsy
dc.subjectMicroglia
dc.subjectPurines
dc.subjectTranscriptomics
dc.subjectGenómica Funcional e Estrutural
dc.titlePurinergic exposure induces epigenomic and transcriptomic-mediated preconditioning resembling epilepsy-associated microglial statespor
dc.typeresearch article
dspace.entity.typePublication
oaire.awardTitleEpigenetic regulation of signalling pathways in MTLE-HS and its impact on epileptogenesis
oaire.awardTitleUnit for Multidisciplinary Research in Biomedicine
oaire.awardTitleUnit for Multidisciplinary Research in Biomedicine
oaire.awardTitleLaboratory for Integrative and Translational Research in Population Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F137900%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00215%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00215%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0064%2F2020/PT
oaire.citation.issue8
oaire.citation.startPage110546
oaire.citation.titleiScience
oaire.citation.volume27
oaire.fundingStreamPOR_NORTE
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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