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Compound screening in human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies.
J Cell Sci
March 2025
Epithelial Cell Biology in ENT Research Group, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Regeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. The mechanisms regulating the proliferation and differentiation of tissue-resident airway basal stem cells remain incompletely understood. To identify compounds that promote human airway basal cell proliferation, we performed phenotype-based compound screening of 1,429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase.
View Article and Find Full Text PDFSARS-CoV-2 infection of human lung ALI cultures reveals basal cells as relevant targets.
J Infect Dis
March 2025
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases, Respiratory Medicine and Critical Care, Berlin, Germany.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets ciliated cells during the initial infection of the upper respiratory tract. Since uncertainties persist regarding other involved epithelial cell types, we here utilized viral replication analysis, single-cell RNA sequencing, and spectral microscopy on infected air-liquid interface cultures of human primary nasal and bronchial epithelial cells to discern cell type proportions in relation to SARS-CoV-2 tropism and immune activation. We revealed that, next to ciliated and secretory cells, SARS-CoV-2 (wild type and lineage B1.
View Article and Find Full Text PDFInflammation and epithelial-mesenchymal transition in a CFTR-depleted human bronchial epithelial cell line revealed by proteomics and human organ-on-a-chip.
FEBS J
March 2025
Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy.
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to chronic, unresolved inflammation of the airways due to uncontrolled recruitment of polymorphonuclear leukocytes (PMNs). Evidence indicates that CFTR loss-of-function, in addition to promoting a pro-inflammatory phenotype, is associated with an increased risk of developing cancer, suggesting that CFTR can exert tumor-suppressor functions. Three-dimensional (3D) in vitro culture models, such as the CF lung airway-on-a-chip, can be suitable for studying PMN recruitment, as well as events of cancerogenesis, that is epithelial cell invasion and migration, in CF.
View Article and Find Full Text PDFIn Vitro Model to Test Therapeutic Agents Against Rhinovirus Infection.
Methods Mol Biol
February 2025
Centre for Inflammation and Lung Research, Lewis Katz Medical School, Temple University, Philadelphia, PA, USA.
To develop an antiviral drug, it is extremely important to have a relevant cell culture model system. The airway epithelial cells lining the conductive airways are the primary target for all three classes of rhinoviruses. However, rhinovirus replication is not very robust in airway epithelial cells; therefore, it does not cause cytopathic effects.
View Article and Find Full Text PDFThe lungs of the finch: three-dimensional pulmonary anatomy of the zebra finch ().
Philos Trans R Soc Lond B Biol Sci
February 2025
Department of Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL 32608, USA.
The avian respiratory system has been an area of biological interest for centuries, with zebra finches () emerging in recent decades as a primary avian model organism popularized across numerous disciplines. The pulmonary system of birds is unique in that air moves unidirectionally through the gas-exchanging lung, and previous works have suggested anatomical constraints within the bronchial network that may be coupled to the inspiratory valving mechanism in Aves. We used µCT-based segmented models to visualize and describe the morphology of the zebra finch lower respiratory system and to examine intra- and interspecific differences of the bronchial tree with the phylogenetically and ecologically different African grey parrot ().
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