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Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.

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dc.contributor.authorCahill, Thomas J
dc.contributor.authorSun, Xin
dc.contributor.authorRavaud, Christophe
dc.contributor.authorVilla del Campo, Cristina
dc.contributor.authorKlaourakis, Konstantinos
dc.contributor.authorLupu, Irina-Elena
dc.contributor.authorLord, Allegra M
dc.contributor.authorBrowne, Cathy
dc.contributor.authorJacobsen, Sten Eirik W
dc.contributor.authorGreaves, David R
dc.contributor.authorJackson, David G
dc.contributor.authorCowley, Sally A
dc.contributor.authorJames, William
dc.contributor.authorChoudhury, Robin P
dc.contributor.authorVieira, Joaquim Miguel
dc.contributor.authorRiley, Paul R
dc.contributor.funderBritish Heart Foundation
dc.contributor.funderBHF Oxbridge Centre of Regenerative Medicine
dc.contributor.funderWellcome Trust
dc.contributor.funderBHF Intermediate Basic Science Research
dc.contributor.funderBritish Council. BIRAX (British Israel Research and Academic Exchange Partnership)
dc.contributor.funderFondation Leducq
dc.date.accessioned2021-08-25T07:19:36Z
dc.date.available2021-08-25T07:19:36Z
dc.date.issued2021-01
dc.description.abstractMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1 + myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThis work was funded by the British Heart Foundation (chair award CH/11/1/28798 and programme grant RG/08/003/25264 to PRR) and supported by the BHF Oxbridge Centre of Regenerative Medicine (RM/13/3/30159); a Wellcome Trust Doctoral Training Fellowship 106334/Z/14/Z to TJC; a Wellcome Trust Four year PhD Studentship 215103/Z/18/Z to KK; a BHF Intermediate Basic Science Research Fellowship FS/19/31/34158 to JMV; a British Israel Research and Academic Exchange Partnership (BIRAX) Grant 13BX14PRET; a Leducq Foundation Transatlantic Network of Excellence Program 14CVD04 and MRC Unit funding to DGJ.es_ES
dc.format.number3es_ES
dc.format.volume148es_ES
dc.identifier.citationDevelopment. 2021; 148(3):dev.194563es_ES
dc.identifier.doi10.1242/dev.194563es_ES
dc.identifier.e-issn1477-9129es_ES
dc.identifier.issn0950-1991es_ES
dc.identifier.journalDevelopment (Cambridge, England)es_ES
dc.identifier.pubmedID33462113es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13308
dc.language.isoenges_ES
dc.publisherThe Company of Biologistses_ES
dc.relation.publisherversionhttps://doi.org/10.1242/dev.194563es_ES
dc.repisalud.institucionCNICes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Control Genético del Desarrollo y Regeneración de Órganoses_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshLymphatic Vesselses_ES
dc.subject.meshAnimalses_ES
dc.subject.meshCX3C Chemokine Receptor 1es_ES
dc.subject.meshCell Adhesiones_ES
dc.subject.meshCell Linees_ES
dc.subject.meshEndothelial Cellses_ES
dc.subject.meshGene Expression Regulation, Developmentales_ES
dc.subject.meshGene Knock-In Techniqueses_ES
dc.subject.meshHeartes_ES
dc.subject.meshHumanses_ES
dc.subject.meshInflammationes_ES
dc.subject.meshLymphangiogenesises_ES
dc.subject.meshMacrophageses_ES
dc.subject.meshMicees_ES
dc.subject.meshMice, Inbred C57BLes_ES
dc.subject.meshOrganogenesises_ES
dc.subject.meshReceptors, Granulocyte-Macrophage Colony-Stimulating Factores_ES
dc.subject.meshYolk Saces_ES
dc.titleTissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublicationd27890c6-5721-4832-a07c-6536c38ae44f
relation.isAuthorOfPublication.latestForDiscoveryd27890c6-5721-4832-a07c-6536c38ae44f
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