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Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes

2022Journal article Open access
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dc.contributor.authorFidalgo, Marta F
dc.contributor.authorFonseca, Catarina
dc.contributor.authorCaldas, Paulo
dc.contributor.authorRaposo, Alexandre
dc.contributor.authorBalboni, Tania
dc.contributor.authorHenao Mišíková, Lenka
dc.contributor.authorGrosso, Ana R.
dc.contributor.authorVasconcelos, Francisca
dc.contributor.authorFranco, Claudio
dc.date.accessioned2022-10-21T14:52:03Z
dc.date.available2022-10-21T14:52:03Z
dc.date.issued2022
dc.description© 2022 Fidalgo et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractAdaptation to breathing is a critical step in lung function and it is crucial for organismal survival. Alveoli are the lung gas exchange units and their development, from late embryonic to early postnatal stages, requires feedbacks between multiple cell types. However, how the crosstalk between the alveolar cell types is modulated to anticipate lung adaptation to breathing is still unclear. Here, we uncovered a synchronous alternative splicing switch in multiple genes in the developing mouse lungs at the transition to birth, and we identified hnRNP A1, Cpeb4, and Elavl2/HuB as putative splicing regulators of this transition. Notably, we found that Vegfa switches from the Vegfa 164 isoform to the longer Vegfa 188 isoform exclusively in lung alveolar epithelial AT1 cells. Functional analysis revealed that VEGFA 188 (and not VEGFA 164) drives the specification of Car4-positive aerocytes, a subtype of alveolar endothelial cells specialized in gas exchanges. Our results reveal that the cell type-specific regulation of Vegfa alternative splicing just before birth modulates the epithelial-endothelial crosstalk in the developing alveoli to promote lung adaptation to breathing.pt_PT
dc.description.sponsorshipThis work was supported by European Research Council (ERC starting grant [679368]), the European Union (H2020-TWINN-2015 – Twinning [692322]), Fundação para a Ciência e Tecnologia (FCT) (PTDC/MED-PAT/31639/2017, and UIDP/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO), and Fondation Leducq (17CVD03). CG Fonseca was supported by a PhD fellowship from the doctoral program Bioengineering: Cellular Therapies and Regenerative Medicine funded by Fundação para a Ciência e Tecnologia (FCT) (PD/BD/128375/2017). T Balboni was supported by a PhD fellowship from the doctoral program “Oncology, Hematology and Pathology - 30th Cycle” funded by University of Bologna, Italy. P Caldas was supported by a postdoctoral researcher fellowship from FCT (PTDC/MED-ONC/28660/2017). AASF Raposo was supported by FCT and Fundo Europeu de Desenvolvimento Regional (FEDER) PAC-PRECISE-LISBOA-01-0145-FEDER-016394 and by an assistant researcher contract from FCT (CEECIND/01474/2017). AR Grosso was supported by a principal investigator contract from FCT (CEECIND/02699/2017). FF Vasconcelos was supported by a postdoctoral researcher contract from FCT (CEECIND/04251/2017). CA Franco was supported by a principal investigator contract from FCT (CEECIND/02589/2018).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLife Sci Alliance. 2022 Oct 11;5(12):e20220155pt_PT
dc.identifier.doi10.26508/lsa.202201554pt_PT
dc.identifier.issn2575-1077
dc.identifier.urihttp://hdl.handle.net/10451/54850
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherLife Science Alliance LLC.pt_PT
dc.relationPAC-PRECISE-LISBOA-01-0145-FEDER-016394pt_PT
dc.relationPRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
dc.relationTowards outstanding research and training in tumour biology at IMM
dc.relationDeregulated Endothelial Blood Flow Response as a cause of Diabetic Retinopathy
dc.relationApplied Molecular Biosciences Unit
dc.relationBiomechanics of vascular remodelling
dc.relationNot Available
dc.relationNot Available
dc.relationNot Available
dc.relationNot Available
dc.relation.publisherversionhttps://www.life-science-alliance.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleAerocyte specification and lung adaptation to breathing is dependent on alternative splicing changespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
oaire.awardTitleTowards outstanding research and training in tumour biology at IMM
oaire.awardTitleDeregulated Endothelial Blood Flow Response as a cause of Diabetic Retinopathy
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleBiomechanics of vascular remodelling
oaire.awardTitleNot Available
oaire.awardTitleNot Available
oaire.awardTitleNot Available
oaire.awardTitleNot Available
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/679368/EU
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oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND%2F02589%2F2018%2FCP1543%2FCT0005/PT
oaire.citation.issue12pt_PT
oaire.citation.startPagee202201554pt_PT
oaire.citation.titleLife Science Alliancept_PT
oaire.citation.volume5pt_PT
oaire.fundingStreamH2020
oaire.fundingStreamH2020
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStreamCEEC IND 2017
oaire.fundingStreamCEEC IND 2017
oaire.fundingStreamCEEC IND 2017
oaire.fundingStreamCEEC IND 2018
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rcaap.typearticlept_PT
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