Project description:Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with DNAH5 mutation. We found abnormal ciliary function and a decreased immune response caused by DNAH5 mutation through proteomic analyses.
Project description:Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with DNAH5 mutation. We found abnormal ciliary function and a decreased immune response caused by DNAH5 mutation through single-cell RNA sequencing (scRNA-seq).
2022-11-12 | GSE217596 | GEO
Project description:Airway microbiota correlated with pulmonary exacerbation in primary ciliary dyskinesia patients
Project description:Submerged cultures of undifferentiated or transformed epithelial cells are widely used in respiratory research due to their ease of use and scalability. However, these systems fail to capture the cellular diversity of the human airway epithelium. Here, we describe a submerged differentiation model using cryopreserved human nasal epithelial cells obtained via minimally invasive brushings. By targeting Notch and BMP signaling with small-molecule inhibitors, we differentiate these cells into complex epithelial cultures containing basal, secretory, and ciliated cell types on standard plastic cultureware. This method supports scalable culturing of both 2D epithelial monolayers and 3D organoids, and is applied to disease modeling in primary ciliary dyskinesia, cystic fibrosis, and respiratory syncytial virus infection. The resulting system enables scalable assessment of disease-relevant epithelial functions in respiratory research
Project description:Submerged cultures of undifferentiated or transformed epithelial cells are widely used in respiratory research due to their ease of use and scalability. However, these systems fail to capture the cellular diversity of the human airway epithelium. Here, we describe a submerged differentiation model using cryopreserved human nasal epithelial cells obtained via minimally invasive brushings. By targeting Notch and BMP signaling with small-molecule inhibitors, we differentiate these cells into complex epithelial cultures containing basal, secretory, and ciliated cell types on standard plastic cultureware. This method supports scalable culturing of both 2D epithelial monolayers and 3D organoids, and is applied to disease modeling in primary ciliary dyskinesia, cystic fibrosis, and respiratory syncytial virus infection. The resulting system enables scalable assessment of disease-relevant epithelial functions in respiratory research
