dc.contributor.author | Walter, Wencke | |
dc.contributor.author | Alonso-Herranz, Laura | |
dc.contributor.author | Trappetti, Verdiana | |
dc.contributor.author | Crespo, Isaac | |
dc.contributor.author | Ibberson, Mark | |
dc.contributor.author | Cedenilla, Marta | |
dc.contributor.author | Karaszewska, Anna | |
dc.contributor.author | Nunez, Vanessa | |
dc.contributor.author | Xenarios, Ioannis | |
dc.contributor.author | Arroyo, Alicia G | |
dc.contributor.author | Sanchez-Cabo, Fatima | |
dc.contributor.author | Ricote, Mercedes | |
dc.date.accessioned | 2018-11-22T08:10:52Z | |
dc.date.available | 2018-11-22T08:10:52Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000429866600024 | |
dc.identifier.citation | Cell Rep. 2018; 23(2):622-636 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6677 | |
dc.description.abstract | Macrophage 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.sponsorship | We 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.iso | eng | |
dc.publisher | Cell Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Deciphering the Dynamic Transcriptional and Post-transcriptional Networks of Macrophages in the Healthy Heart and after Myocardial Injury | |
dc.type | journal article | |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 29642017 | |
dc.format.volume | 23 | |
dc.format.page | 622-636 | |
dc.identifier.doi | 10.1016/j.celrep.2018.03.029 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Fundación La Caixa | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2018.03.029 | |
dc.identifier.journal | Cell Reports | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Metaloproteinasas de Matriz en Angiogénesis e Inflamación | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Señalización de los Receptores Nucleares | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Bioinformática | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2015-64287R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2015-71878-REDT | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/608027/EU | es_ES |
dc.rights.accessRights | open access | es_ES |