Sistema de Salut de Catalunya
Institut Català de la Salut
[Serapiglia V] School of Medicine, Northeast Ohio College of Medicine, Northeast Ohio Medical University, Rootstown Township, OH, United States. [Stephens CA] Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States. [Joshi R] Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. [Aydin E] Department of Pediatric Surgery, Tekirdag Namik Kemal University School of Medicine, Tekirdag, Turkey. Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, United States. [Oria M, Peiro JL] Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, United States. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United States. [Marotta M] Laboratori de Bioenginyeria, Teràpia Cel•lular i Cirurgia en Malformacions Congènites, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Varisco BM] Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
Vall d'Hebron Barcelona Hospital Campus
2022-07-25T09:51:50Z
2022-07-25T09:51:50Z
2022-02-22
Basal cell; Fetal tracheal occlusion; Mechanotransduction
Célula basal; Oclusión traqueal fetal; Mecanotransducción
Cèl·lula basal; Oclusió traqueal fetal; Mecanotransducció
Fetal endoscopic tracheal occlusion (FETO) is an emerging surgical therapy for congenital diaphragmatic hernia (CDH). Ovine and rabbit data suggested altered lung epithelial cell populations after tracheal occlusion (TO) with transcriptomic signatures implicating basal cells. To test this hypothesis, we deconvolved mRNA sequencing (mRNA-seq) data and used quantitative image analysis in fetal rabbit lung TO, which had increased basal cells and reduced ciliated cells after TO. In a fetal mouse TO model, flow cytometry showed increased basal cells, and immunohistochemistry demonstrated basal cell extension to subpleural airways. Nuclear Yap, a known regulator of basal cell fate, was increased in TO lung, and Yap ablation on the lung epithelium abrogated TO-mediated basal cell expansion. mRNA-seq of TO lung showed increased activity of downstream Yap genes. Human lung specimens with congenital and fetal tracheal occlusion had clusters of subpleural basal cells that were not present in the control. TO increases lung epithelial cell nuclear Yap, leading to basal cell expansion.
Funding was obtained from NIH/NHLBI R01HL141229 (to BV).
Article
Published version
English
Malalties congènites - Tractament; Hèrnia - Tractament; DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Hernias, Diaphragmatic, Congenital; Other subheadings::Other subheadings::Other subheadings::/therapy; ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::hernias diafragmáticas congénitas; Otros calificadores::Otros calificadores::Otros calificadores::/terapia
Frontiers Media
Frontiers in Pediatrics;9
https://doi.org/10.3389/fped.2021.780166
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - VHIR [1655]
