Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.14/39228 |
Resumo: | 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. |
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Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changesAdaptation 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.Veritati - Repositório Institucional da Universidade Católica PortuguesaFidalgo, Marta F.Fonseca, Catarina G.Caldas, PauloRaposo, Alexandre A. S. F.Balboni, TaniaHenao-Mišíková, LenkaGrosso, Ana R.Vasconcelos, Francisca F.Franco, Cláudio A.2022-11-02T17:16:19Z2022-12-012022-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/39228eng2575-107710.26508/lsa.20220155485139692081PMC955479636220570000966879400002info: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:RCAAP2024-01-09T01:36:23Zoai:repositorio.ucp.pt:10400.14/39228Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:32:03.953179Repositório 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 G. Caldas, Paulo Raposo, Alexandre A. S. F. Balboni, Tania Henao-Mišíková, Lenka Grosso, Ana R. Vasconcelos, Francisca F. Franco, Cláudio A. |
author_role |
author |
author2 |
Fonseca, Catarina G. Caldas, Paulo Raposo, Alexandre A. S. F. Balboni, Tania Henao-Mišíková, Lenka Grosso, Ana R. Vasconcelos, Francisca F. Franco, Cláudio A. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Veritati - Repositório Institucional da Universidade Católica Portuguesa |
dc.contributor.author.fl_str_mv |
Fidalgo, Marta F. Fonseca, Catarina G. Caldas, Paulo Raposo, Alexandre A. S. F. Balboni, Tania Henao-Mišíková, Lenka Grosso, Ana R. Vasconcelos, Francisca F. Franco, Cláudio A. |
description |
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. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-02T17:16:19Z 2022-12-01 2022-12-01T00:00:00Z |
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/10400.14/39228 |
url |
http://hdl.handle.net/10400.14/39228 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2575-1077 10.26508/lsa.202201554 85139692081 PMC9554796 36220570 000966879400002 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132044556500992 |