Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling
Serapiglia, Vincent (Northeast Ohio Medical University)
Stephens, Chad A. (University of Illinois at Chicago)
Joshi, Rashika (Cincinnati Children's Hospital Medical Center)
Aydin, Emrah (Cincinnati Children's Hospital Medical Center)
Oria Alonso, Marc (University of Cincinnati)
Marotta, Mario (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Peiro, Jose L. (University of Cincinnati)
Varisco, Brian M. (University of Cincinnati)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Fetal tracheal occlusion ; Congenital diaphragm hernia ; Lung development ; Basal cell ; Yap (Hippo) signaling ; Mechanotransduction
Publicado en:	Frontiers in Pediatrics, Vol. 9 (february 2022) , ISSN 2296-2360

DOI: 10.3389/fped.2021.780166
PMID: 35280447

12 p, 3.7 MB

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