Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical-basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2.
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http://dx.doi.org/10.1083/jcb.201506014 | DOI Listing |
Biosensors (Basel)
November 2024
Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.
Organ-on-a-chip (OOC) devices mimic human organs, which can be used for many different applications, including drug development, environmental toxicology, disease models, and physiological assessment. Image data acquisition and analysis from these chips are crucial for advancing research in the field. In this study, we propose a label-free morphology imaging platform compatible with the small airway-on-a-chip system.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria.
Introduction: Airway epithelial cells play a central role in the innate immune response to invading bacteria, yet adequate human infection models are lacking.
Methods: We utilized mucociliary-differentiated human airway organoids with direct access to the apical side of epithelial cells to model the initial phase of respiratory tract infection.
Results: Immunofluorescence of infected organoids revealed that invades the epithelial barrier and subsequently proliferates within the epithelial space.
Physiol Res
November 2024
Department of Histology and Embryology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Lab Anim (NY)
December 2024
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
Nat Commun
November 2024
Department of Cell & Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
SARS-CoV-2 initiates infection in the conducting airways, where mucociliary clearance inhibits pathogen penetration. However, it is unclear how mucociliary clearance impacts SARS-CoV-2 spread after infection is established. To investigate viral spread at this site, we perform live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 12 days.
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