Show simple item record

dc.contributor.authorWalter, Wencke 
dc.contributor.authorAlonso-Herranz, Laura 
dc.contributor.authorTrappetti, Verdiana 
dc.contributor.authorCrespo, Isaac 
dc.contributor.authorIbberson, Mark
dc.contributor.authorCedenilla, Marta 
dc.contributor.authorKaraszewska, Anna 
dc.contributor.authorNunez, Vanessa 
dc.contributor.authorXenarios, Ioannis
dc.contributor.authorArroyo, Alicia G 
dc.contributor.authorSanchez-Cabo, Fatima 
dc.contributor.authorRicote, Mercedes 
dc.date.accessioned2018-11-22T08:10:52Z
dc.date.available2018-11-22T08:10:52Z
dc.date.issued2018
dc.identifierISI:000429866600024
dc.identifier.citationCell Rep. 2018; 23(2):622-636
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6677
dc.description.abstractMacrophage plasticity has been studied in vitro, but transcriptional regulation upon injury is poorly understood. We generated a valuable dataset that captures transcriptional changes in the healthy heart and after myocardial injury, revealing a dynamic transcriptional landscape of macrophage activation. Partial deconvolution suggested that post-injury macrophages exhibit overlapping activation of pro-inflammatory and anti-inflammatory programs rather than aligning to canonical M1/M2 programs. Furthermore, simulated dynamics and experimental validation of a regulatory core of the underlying gene-regulatory network revealed a negative-feedback loop that limits initial inflammation via hypoxia-mediated upregulation of ll10. Our results also highlight the prominence of post-transcriptional regulation (miRNAs, mRNA decay, and lincRNAs) in attenuating the myocardial injury-induced inflammatory response. We also identified a cardiac-macrophage-specific gene signature (e.g., Egfr and Lifr) and time-specific markers for macrophage populations (e.g., Lyve1, Cd40, and Mrc1). Altogether, these data provide a core resource for deciphering the transcriptional network in cardiac macrophages in vivo.
dc.description.sponsorshipWe thank S. Bartlett (CNIC) for editorial assistance and the CNIC Cellomics and Genomics Units for technical help. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2015-64287R and SAF2015-71878-REDT) to M.R., and Fundacion Marato TV3 (121931) and the European Commission FP7 (CardioNext-ITN-608027) to M.R. and A.G.A. L.A.-H. is funded by a fellowship from La Caixa-CNIC. The CNIC is supported by MEIC and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).
dc.language.isoeng
dc.publisherCell Press
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleDeciphering the Dynamic Transcriptional and Post-transcriptional Networks of Macrophages in the Healthy Heart and after Myocardial Injury
dc.typeArtículo
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID29642017
dc.format.volume23
dc.format.page622-636
dc.identifier.doi10.1016/j.celrep.2018.03.029
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderFundacio La Marato
dc.contributor.funderEuropean Commission
dc.contributor.funderFundación La Caixa
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderFundación ProCNIC
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2018.03.029
dc.identifier.journalCell Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Metaloproteinasas de Matriz en Angiogénesis e Inflamación
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización de los Receptores Nucleares
dc.repisalud.orgCNICCNIC::Unidades técnicas::Bioinformática
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-64287Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-71878-REDTes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/608027/EUes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional