This SuperSeries is composed of the SubSeries listed below.
Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
Sex, Age, Race
View SamplesBackground: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting cilia length must exceed the 6 -7 m airway surface fluid depth to generate force in the mucus layer, we hypothesized cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers.
Smoking is associated with shortened airway cilia.
Sex, Age
View SamplesUpregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers
Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
Sex, Age
View SamplesResponses of the Human Airway Epithelium Transcriptome to In Vivo Injury
Responses of the human airway epithelium transcriptome to in vivo injury.
Sex, Age, Time
View SamplesModification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking
Modification of gene expression of the small airway epithelium in response to cigarette smoking.
Sex, Age
View SamplesAirway remodelling in chronic obstructive pulmonary disease (COPD) originates, in part, from smoking-induced changes in airway basal stem/progenitor cells (BCs). Based on the knowledge that bone morphogenetic protein 4 (BMP4) influences epithelial progenitor function in the developing and adult mouse lung, we hypothesised that BMP4 signalling may regulate the biology of adult human airway BCs relevant to COPD.
Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium.
Specimen part
View SamplesBackground: High mobility group AT-hook1 (HMGA1) is essential for airway basal cell mucociliary differentiation, barrier integrity and wound repair. HMGA1 expression suppresses the abnormal basal cell differentiation to squamous, inflammatory and epithelial-mesenchymal transition phenotype commonly observed in association with cigarette smoking and chronic obstructive pulmonary disease (COPD). Results: HMGA1 knockdown experiments indicate that when HMGA1 expression is suppressed, the airway basal cells cannot normally differentiate into a mucociliary epithelium, form an intact barrier, and repair following injury. Instead, airway basal cell differentiation was skewed to an abnormal squamous EMT-like phenotype associated with airway remodeling in COPD. This study demonstrates that HMGA1 plays a key role in normal airway differentiation, regeneration of the normal airway epithelium following injury, and suppression of expression of genes related to squamous metaplasia, EMT and inflammation. Overall design: [RNA-seq] Non-smoker large airway epithelium cells, large airway basal cells, small airway epithelial cells, small airway basal cells. Smoker large airway basal cells, COPD smoker large airway basal cells,.
Mandatory role of HMGA1 in human airway epithelial normal differentiation and post-injury regeneration.
Specimen part, Subject
View SamplesThe pathology of chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and the majority of lung cancers involve the small airway epithelium (SAE), the single continuous layer of cells lining the airways ?6th generations. The basal cells (BC) are the stem/progenitor cells of the SAE, responsible for the differentiation into intermediate cells and ciliated, club and mucous differentiated cells. To facilitate the study of the biology of the human SAE in health and disease, we immortalized and characterized a normal human SAE basal cell line.
Characterization of an immortalized human small airway basal stem/progenitor cell line with airway region-specific differentiation capacity.
Sex, Age, Specimen part, Race
View SamplesDiabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. Here we report the development of a 3D blood vessel organoid culture system from human pluripotent stem cells. These human blood vessel organoids contain endothelial cells and pericytes that self-assemble into interconnected capillary networks enveloped by a basement membrane. Human blood vessel organoids transplanted into mice form a stable, perfused human vascular tree, including human arteries, arterioles and venules. Exposure of blood vessel organoids to hyperglycemia and inflammatory cytokines in vitro induced thickening of the basal membrane, a hallmark of human diabetic microangiopathy. Human blood vessel, exposed in vivo to a diabetic milieu in mice, also mimick the microvascular changes in diabetic patients. We finally performed a drug screen and uncovered ?-secretase and DLL4-Notch3 as key drivers of “diabetic” vasculopathy in human blood vessels in vitro and in vivo. Thus, organoids derived from human stem cells faithfully recapitulate the structure and function of human blood vessels and are amenable to model and identify drug targets for diabetic vasculopathy, which affects hundreds of millions of patients. Overall design: Vascular organoids were differentiated from iPSC cells and cultured in control, diabetic or diabetic media supplemented with the gamma-secretase inhibitor DAPT. Endothelial cells (CD31 positive) and pericytes (PDGFRbeta positive) were isolated by FACS and subjected to RNA Seq. Accordingly, CD31 positive endothelial cells and PDGFRbeta positive pericytes differentiated from iPS cells in 2D as a well as primary endothelial (HUVECS) and pericytes (Placenta) were FACS sorted and subjected to RNA Seq.
Human blood vessel organoids as a model of diabetic vasculopathy.
Sex, Specimen part, Cell line, Subject
View SamplesDiabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. We report the development of 3D blood vessel organoids from human embryonic and induced pluripotent stem cells. These human blood vessel organoids contain endothelium, perivascular pericytes, and basal membranes, and self-assemble into lumenized interconnected capillary networks. We treat these vascular organoids with hyperglycemia and inflammatory cytokines in vitro, which leads to basement membrane thickening, a structural hallmark of diabetic patient. To compare differential gene expression we performed RNAseq on endothelial cells, derived from control (NG) or diabetic (DI) vascular organoids. Overall design: Vascular organoids were differentiated from human iPS cells and treated for 3 weeks with a diabetic media containing 75mM Glucose, 1ng/mL TNF-a, 1ng/mL IL6 (DI) or left untreated in 17mM Glucose (NG). Endothelial cells were FACS sorted for CD31 directly into Trizol and stored at -80°C before RNA preparation. The 2 NG and 2 DI are pools of sorted endothelial cells from multiple vascular organoids (>100) from 2 independent differentiations/treatments.
Human blood vessel organoids as a model of diabetic vasculopathy.
Sex, Specimen part, Cell line, Subject
View Samples