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

dc.contributor.authorFidalgo, Marta F.
dc.contributor.authorFonseca, Catarina G.
dc.contributor.authorCaldas, Paulo
dc.contributor.authorRaposo, Alexandre A. S. F.
dc.contributor.authorBalboni, Tania
dc.contributor.authorHenao-Mišíková, Lenka
dc.contributor.authorGrosso, Ana R.
dc.contributor.authorVasconcelos, Francisca F.
dc.contributor.authorFranco, Cláudio A.
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDCV - Departamento de Ciências da Vida
dc.contributor.pblRockefeller University Press
dc.date.accessioned2023-03-10T22:54:41Z
dc.date.available2023-03-10T22:54:41Z
dc.date.issued2022-12
dc.descriptionFunding Information: ariana Ferreira, Marie Bordone, Nuno Agostinho and Nuno Barbosa Morais (Disease Transcriptomics Lab, iMM) for input on bioinformatics analysis. Pedro Papotto, Karine Serre (Immuno-Biology & Immuno-Oncology Lab, iMM), Idálio Viegas (Biology of Parasitism Lab, iMM), Isabel Alcobia (Institute of Histology and Developmental Biology, FMUL), Debanjan Mukherjee, Vanessa Zuzarte-Luís (Biology & Physiology of Malaria, iMM), and Mahak Singhal (Vascular Oncology and Metastasis Division, DKFZ), for input on experimental protocols. Luís Oliveira (Cell Architecture Lab, iMM) for input on microscopy image analysis. Flow Cytometry, Bioimaging, Rodent and Comparative Pathology Units at iMM for technical support. All members of the Vascular Morphogenesis lab at iMM for discussions, helpful input and for carefully reviewing the manuscript. Nuno Barbosa Morais for carefully reading this manuscript and providing helpful and critical feedback. This work was supported by the Fondation Leducq (17CVD03). T Balboni was supported by a PhD fellowship from the doctoral program “Oncology, Hematology and Pathology - 30th Cycle” funded by University of Bologna, Italy. AASF Raposo was supported by FCT and Fundo Europeu de Desenvolvimento Regional (FEDER) PAC-PRECISE-LISBOA-01-0145-FEDER-016394. Publisher Copyright: © 2022 Fidalgo et al.
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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent25
dc.format.extent3558050
dc.identifier.doi10.26508/lsa.202201554
dc.identifier.otherPURE: 55291958
dc.identifier.otherPURE UUID: dda52c98-88e2-4fbb-9a30-a09be251401a
dc.identifier.otherScopus: 85139692081
dc.identifier.otherPubMed: 36220570
dc.identifier.otherPubMedCentral: PMC9554796
dc.identifier.otherORCID: /0000-0001-6974-4209/work/130607675
dc.identifier.urihttp://hdl.handle.net/10362/150363
dc.identifier.urlhttps://www.scopus.com/pages/publications/85139692081
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/679368/EU
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.relationinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F01474%2F2017%2FCP1396%2FCT0003/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F02699%2F2017%2FCP1462%2FCT0018/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F04251%2F2017%2FCP1396%2FCT0010/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND%2F02589%2F2018%2FCP1543%2FCT0005/PT
dc.subjectEcology
dc.subjectBiochemistry, Genetics and Molecular Biology (miscellaneous)
dc.subjectPlant Science
dc.subjectHealth, Toxicology and Mutagenesis
dc.titleAerocyte specification and lung adaptation to breathing is dependent on alternative splicing changesen
dc.typejournal article
degois.publication.issue12
degois.publication.titleLife Science Alliance
degois.publication.volume5
dspace.entity.typePublication
oaire.awardNumber679368
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oaire.awardNumberCEECIND/04251/2017/CP1396/CT0010
oaire.awardNumberCEECIND/02589/2018/CP1543/CT0005
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
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oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F01474%2F2017%2FCP1396%2FCT0003/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F02699%2F2017%2FCP1462%2FCT0018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F04251%2F2017%2FCP1396%2FCT0010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND%2F02589%2F2018%2FCP1543%2FCT0005/PT
oaire.fundingStreamH2020
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oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStreamCEEC IND 2017
oaire.fundingStreamCEEC IND 2017
oaire.fundingStreamCEEC IND 2017
oaire.fundingStreamCEEC IND 2018
project.funder.identifierhttp://doi.org/10.13039/501100008530
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project.funder.nameEuropean Commission
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