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Loss of Ccbe1 affects cardiac-specification and cardiomyocyte differentiation in mouse embryonic stem cells

2018-10Journal article Open access
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dc.contributor.authorBover, Oriol
dc.contributor.authorJusto, Tiago
dc.contributor.authorPereira, Paulo N. G.
dc.contributor.authorFacucho-Oliveira, João
dc.contributor.authorInácio, José M.
dc.contributor.authorRamalho, José S.
dc.contributor.authorDomian, Ibrahim J.
dc.contributor.authorBelo, José A.
dc.date.accessioned2018-12-07T14:58:06Z
dc.date.available2018-12-07T14:58:06Z
dc.date.issued2018-10
dc.description.abstractUnderstanding the molecular pathways regulating cardiogenesis is crucial for the early diagnosis of heart diseases and improvement of cardiovascular disease. During normal mammalian cardiac development, collagen and calcium-binding EGF domain-1 (Ccbe1) is expressed in the first and second heart field progenitors as well as in the proepicardium, but its role in early cardiac commitment remains unknown. Here we demonstrate that during mouse embryonic stem cell (ESC) differentiation Ccbe1 is upregulated upon emergence of Isl1- and Nkx2.5- positive cardiac progenitors. Ccbe1 is markedly enriched in Isl1-positive cardiac progenitors isolated from ESCs differentiating in vitro or embryonic hearts developing in vivo. Disruption of Ccbe1 activity by shRNA knockdown or blockade with a neutralizing antibody results in impaired differentiation of embryonic stem cells along the cardiac mesoderm lineage resulting in a decreased expression of mature cardiomyocyte markers. In addition, knockdown of Ccbe1 leads to smaller embryoid bodies. Collectively, our results show that CCBE1 is essential for the commitment of cardiac mesoderm and consequently, for the formation of cardiac myocytes in differentiating mouse ESCs.
dc.description.sponsorshipFundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/82280/2011]; FCT [SFRH/BPD/46506/2008, CEDOC/2015/36/iNOVA4Health/Multi/04462, SFRH/BPD/87114/2012, PTDC/SAU-ENB/121095/2010, HMSP-ICT/0039/2013]; Fundacao para a Ciencia e Tecnologia / Ministerio da Educacao e Ciencia [UID/Multi/04462/2013]; FEDER under the PT2020 Partnership Agreement
dc.identifier.doi10.1371/journal.pone.0205108
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11856
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library Science
dc.relationROLE OF CCBE1 DURING CARDIAC DIFFERENTIATION OF MOUSE ES CELLS
dc.relationSTUDY OF THE ROLE OF A NOVEL GENE CODING FOR A CALCIUM-BINDING EGF-LIKE DOMAIN PROTEIN IN THE PROCESS OF INDUCTION AND ORGANOGENESIS OF THE HEART
dc.relationiNOVA4Health - Programme in Translational Medicine (iBET, CEDOC/FCM, IPOLFG and ITQB)
dc.relationROLE OF CCBE1 DURING HEART DEVELOPMENT IN MICE AND MESC-DERIVED CARDIAC CELLS
dc.relationEstudo do papel do novo factor de crescimento Ccbe1 na criação de tecido cardíaco apartir de células ES
dc.subjectCcbe1
dc.subjectLymphangiogenesis
dc.subjectProgenitors
dc.subjectInduction
dc.subjectMutations
dc.subjectDysplasia
dc.subjectLineages
dc.subjectVegfc
dc.titleLoss of Ccbe1 affects cardiac-specification and cardiomyocyte differentiation in mouse embryonic stem cells
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleROLE OF CCBE1 DURING CARDIAC DIFFERENTIATION OF MOUSE ES CELLS
oaire.awardTitleSTUDY OF THE ROLE OF A NOVEL GENE CODING FOR A CALCIUM-BINDING EGF-LIKE DOMAIN PROTEIN IN THE PROCESS OF INDUCTION AND ORGANOGENESIS OF THE HEART
oaire.awardTitleiNOVA4Health - Programme in Translational Medicine (iBET, CEDOC/FCM, IPOLFG and ITQB)
oaire.awardTitleROLE OF CCBE1 DURING HEART DEVELOPMENT IN MICE AND MESC-DERIVED CARDIAC CELLS
oaire.awardTitleEstudo do papel do novo factor de crescimento Ccbe1 na criação de tecido cardíaco apartir de células ES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F82280%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F46506%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04462%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F87114%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-ENB%2F121095%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0039%2F2013/PT
oaire.citation.issue10
oaire.citation.startPagee0205108
oaire.citation.titlePlos One
oaire.citation.volume13
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
person.familyNameJusto
person.familyNameFacucho-Oliveira
person.familyNameBelo
person.givenNameTiago
person.givenNameJoão
person.givenNameJosé A.
person.identifier.ciencia-id9B18-CDAE-64B0
person.identifier.ciencia-idBF13-08E9-25E6
person.identifier.orcid0000-0002-8763-8677
person.identifier.orcid0000-0003-2940-7915
person.identifier.orcid0000-0001-7384-0949
person.identifier.ridF-4444-2012
person.identifier.scopus-author-id54079746100
person.identifier.scopus-author-id6602141392
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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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
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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