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

Detalhes bibliográficos
Autor(a) principal: Fidalgo, Marta F
Data de Publicação: 2022
Outros Autores: Fonseca, Catarina, Caldas, Paulo, Raposo, Alexandre, Balboni, Tania, Henao Mišíková, Lenka, Grosso, Ana R., Vasconcelos, Francisca, Franco, Claudio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/54850
Resumo: © 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/).
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spelling Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes© 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/).Adaptation 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.This 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).Life Science Alliance LLC.Repositório da Universidade de LisboaFidalgo, Marta FFonseca, CatarinaCaldas, PauloRaposo, AlexandreBalboni, TaniaHenao Mišíková, LenkaGrosso, Ana R.Vasconcelos, FranciscaFranco, Claudio2022-10-21T14:52:03Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54850engLife Sci Alliance. 2022 Oct 11;5(12):e202201552575-107710.26508/lsa.202201554info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:01:31Zoai:repositorio.ul.pt:10451/54850Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:37.064205Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
title Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
spellingShingle Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
Fidalgo, Marta F
title_short Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
title_full Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
title_fullStr Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
title_full_unstemmed Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
title_sort Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
author Fidalgo, Marta F
author_facet Fidalgo, Marta F
Fonseca, Catarina
Caldas, Paulo
Raposo, Alexandre
Balboni, Tania
Henao Mišíková, Lenka
Grosso, Ana R.
Vasconcelos, Francisca
Franco, Claudio
author_role author
author2 Fonseca, Catarina
Caldas, Paulo
Raposo, Alexandre
Balboni, Tania
Henao Mišíková, Lenka
Grosso, Ana R.
Vasconcelos, Francisca
Franco, Claudio
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Fidalgo, Marta F
Fonseca, Catarina
Caldas, Paulo
Raposo, Alexandre
Balboni, Tania
Henao Mišíková, Lenka
Grosso, Ana R.
Vasconcelos, Francisca
Franco, Claudio
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/).
publishDate 2022
dc.date.none.fl_str_mv 2022-10-21T14:52:03Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54850
url http://hdl.handle.net/10451/54850
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Life Sci Alliance. 2022 Oct 11;5(12):e20220155
2575-1077
10.26508/lsa.202201554
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Life Science Alliance LLC.
publisher.none.fl_str_mv Life Science Alliance LLC.
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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