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YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1

Ventilation is dependent upon pulmonary alveoli lined by two major epithelial cell types, alveolar type-1 (AT1) and 2 (AT2) cells. AT1 cells mediate gas exchange while AT2 cells synthesize and secrete pulmonary surfactants and serve as progenitor cells which repair the alveoli. We developed transgen...

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Detalles Bibliográficos
Autores principales: Gokey, Jason J., Snowball, John, Sridharan, Anusha, Sudha, Parvathi, Kitzmiller, Joseph A., Xu, Yan, Whitsett, Jeffrey A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383002/
https://www.ncbi.nlm.nih.gov/pubmed/34466790
http://dx.doi.org/10.1016/j.isci.2021.102967
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author Gokey, Jason J.
Snowball, John
Sridharan, Anusha
Sudha, Parvathi
Kitzmiller, Joseph A.
Xu, Yan
Whitsett, Jeffrey A.
author_facet Gokey, Jason J.
Snowball, John
Sridharan, Anusha
Sudha, Parvathi
Kitzmiller, Joseph A.
Xu, Yan
Whitsett, Jeffrey A.
author_sort Gokey, Jason J.
collection PubMed
description Ventilation is dependent upon pulmonary alveoli lined by two major epithelial cell types, alveolar type-1 (AT1) and 2 (AT2) cells. AT1 cells mediate gas exchange while AT2 cells synthesize and secrete pulmonary surfactants and serve as progenitor cells which repair the alveoli. We developed transgenic mice in which YAP was activated or deleted to determine its roles in alveolar epithelial cell differentiation. Postnatal YAP activation increased epithelial cell proliferation, increased AT1 cell numbers, and caused indeterminate differentiation of subsets of alveolar cells expressing atypical genes normally restricted to airway epithelial cells. YAP deletion increased expression of genes associated with mature AT2 cells. YAP activation enhanced DNA accessibility in promoters of transcription factors and motif enrichment analysis predicted target genes associated with alveolar cell differentiation. YAP participated with KLF5, NFIB, and NKX2-1 to regulate AGER. YAP plays a central role in a transcriptional network that regulates alveolar epithelial differentiation.
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spelling pubmed-83830022021-08-30 YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1 Gokey, Jason J. Snowball, John Sridharan, Anusha Sudha, Parvathi Kitzmiller, Joseph A. Xu, Yan Whitsett, Jeffrey A. iScience Article Ventilation is dependent upon pulmonary alveoli lined by two major epithelial cell types, alveolar type-1 (AT1) and 2 (AT2) cells. AT1 cells mediate gas exchange while AT2 cells synthesize and secrete pulmonary surfactants and serve as progenitor cells which repair the alveoli. We developed transgenic mice in which YAP was activated or deleted to determine its roles in alveolar epithelial cell differentiation. Postnatal YAP activation increased epithelial cell proliferation, increased AT1 cell numbers, and caused indeterminate differentiation of subsets of alveolar cells expressing atypical genes normally restricted to airway epithelial cells. YAP deletion increased expression of genes associated with mature AT2 cells. YAP activation enhanced DNA accessibility in promoters of transcription factors and motif enrichment analysis predicted target genes associated with alveolar cell differentiation. YAP participated with KLF5, NFIB, and NKX2-1 to regulate AGER. YAP plays a central role in a transcriptional network that regulates alveolar epithelial differentiation. Elsevier 2021-08-11 /pmc/articles/PMC8383002/ /pubmed/34466790 http://dx.doi.org/10.1016/j.isci.2021.102967 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Gokey, Jason J.
Snowball, John
Sridharan, Anusha
Sudha, Parvathi
Kitzmiller, Joseph A.
Xu, Yan
Whitsett, Jeffrey A.
YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1
title YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1
title_full YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1
title_fullStr YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1
title_full_unstemmed YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1
title_short YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1
title_sort yap regulates alveolar epithelial cell differentiation and ager via nfib/klf5/nkx2-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383002/
https://www.ncbi.nlm.nih.gov/pubmed/34466790
http://dx.doi.org/10.1016/j.isci.2021.102967
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