Charaterization club cell lineages in small airways of naïve WT mice
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ABSTRACT:
PROVIDER: PRJNA649211 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mouse small airways are populated by different epithelial lineages that generate from club cell progenitors that can express IL-33 as alarmin which could be released after epithelial injury
2020-07-29 | GSE155261 | GEO
Project description:ATGL= the rate-limiting enzyme for intracellular lipolysis. Atgl KO/cTg = Mice lacking Atgl except for cardiac transgenic overexpression of Atgl (Atgl -/- ,Myh6Atgl+/+) to rescue early age death deu to cardiomyopathy. wt/cTg = respective control. The airways of the lung are constantly exposed to inhaled toxic substances, resulting in cellular damage. Within bronchii, club cells make up majority of the cell population in the terminal bronchiolar epithelia. Club cells are known for their ability to metabolize environmental toxins and constantly repairing small impacts in the epithelial layer. Considering the importance of club cells in maintaining bronchiolar epithelial integrity, we porformed gene expression data analysis to decipher the possible dysregulated gene expression thereby corresponding molecular pathways in our mice lacking ATGL.
2021-05-28 | GSE175659 | GEO
Project description:Gene expression patterns of bronchiolar progenitors and club cells in mouse lung were examined by microarray experiments. Although it has not yet been fully characterized, a subset of epithelial cells lining bronchioles are best understood as bronchiolar progenitors that self-renew over the long term and that can differentiate into more differentiated club cells and ciliated cells. The bronchiolar progenitors are distinct from club cells and characteristically express the alveolar type 2 cell marker, prosurfactant protein C, with lower levels of club cell secretory protein/Scgb1a1. There are also functional differences between them; while club cells can be depleted by naphthalene because of the abundance of cytochrome P450 enzyme Cyp2f2, bronchiolar progenitors are resistant to naphthalene-induced depletion because of defects in the enzyme.
2016-02-17 | E-MTAB-4460 | biostudies-arrayexpress
Project description:Club (“Clara”) cells, dome shaped cells with disease cytoplasmic granules and microvilli, are the major secretory cell of the human small (>6 generation) airways. Little is known regarding the biology of club cells in the human airway, nor of the ontogeny of this cell type. Taking advantage of the SCGB1A1 as the marker for club cells and our ability to sample the normal small airway epithelium by bronchoscopy and brushing healthy volunteers, we defined the transcriptome of the normal human airway club cell using single cell transcriptome sequencing. Analysis of the human small airway epithelial single cell transcriptome together with in vitro validation provides novel insights into the molecular phenotype and biological functions of the human club cell population and identifies the basal cell as the human progenitor cells for club cells.
2024-06-05 | GSE94819 | GEO
Project description:Charaterization of monocytes/macrophages function in Club cell regeneration after naphthalene injury in WT mice
| PRJNA649517 | ENA
Project description:Lung adenocarcinoma (LUAD) is one of the deadliest malignancies worldwide. Dynamic lineage changes within the lung epithelium and the high plasticity of these epithelial cells confound the correct identification of the cell-of-origin of LUAD. Here, we combined lineage-tracing mouse models with an autochthonous cell type-independent LUAD model in order to discover the cellular origin of ALK-translocated LUAD. We identified Club and AT2 cells as the cells-of-origin of LUAD. Moreover, we uncovered epigenetic imprints in the tumours originating from Club or AT2 cells by whole-genome bisulfite sequencing. Single-cell transcriptomes of Club cells at different stages of tumour development identified two trajectories of Club cell evolution. On both routes, tumours lose their Club cell identity and gain an AT2-like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
2022-06-30 | GSE176185 | GEO
Project description:Lung adenocarcinoma (LUAD) is one of the deadliest malignancies worldwide. Dynamic lineage changes within the lung epithelium and the high plasticity of these epithelial cells confound the correct identification of the cell-of-origin of LUAD. Here, we combined lineage-tracing mouse models with an autochthonous cell type-independent LUAD model in order to discover the cellular origin of ALK-translocated LUAD. We identified Club and AT2 cells as the cells-of-origin of LUAD. Moreover, we uncovered epigenetic imprints in the tumours originating from Club or AT2 cells by whole-genome bisulfite sequencing. Single-cell transcriptomes of Club cells at different stages of tumour development identified two trajectories of Club cell evolution. On both routes, tumours lose their Club cell identity and gain an AT2-like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
2022-06-30 | GSE176184 | GEO
Project description:The club cell, a small airway epithelial (SAE) secretory cell that uniquely expresses SCGB1A1, plays a central role in host defense in the human lung. Based on data demonstrating that ~50% of club cells express MUC5B, a secretory mucin critical for mucociliary clearance, we hypothesized that subpopulations of club cells with distinct functions may exist. To evaluate this, the SAE of normal nonsmokers and healthy cigarette smokers was sampled by bronchoscopy and brushing followed by single cell sequencing using Drop-seq technology. Subpopulations of SCGCB1A1+KRT5loMUC5AC- club cells were assessed by unsupervised clustering to evaluate club cell subpopulations. Immunostaining of SAE in lung sections, brushed SAE cells, and in vitro air-liquid interface culture was utilized to confirm the transcriptomic-based observations. Unsupervised clustering of SCGCB1A1+KRT5loMUC5AC‾ club cells in the SAE identified 3 unique club cell populations that differed by differentiation state and function, including: (1) progenitor; (2) proliferating; and (3) effector subpopulations. The progenitor club cell population was energetically active with high expression of mitochondrial and ribosomal proteins and the highest KRT5 levels vs other club cell populations. The proliferating population, defined by high expression of cyclins and proliferation markers, was the smallest, representing 2% of club cells. The effector club cell cluster expressed transcripts for host defense genes, xenobiotic metabo-lism, and barrier functions commonly associated with club cell function. Comparison of the club cell subpopulations in smokers vs nonsmokers demonstrated that the proportion of the club cell effector population was significantly decreased in smokers with a concomitant significant in-crease in the proliferating cell population. These observations provide novel insights into both the makeup of human SAE club cell subpopulations and smoking-induced changes in club cell biology.
2021-09-22 | GSE155515 | GEO
Project description:Charaterization of function of ST2 receptor on macrophages function during Club cell regeneration after naphthalene injury in WT mice
| PRJNA649519 | ENA
Project description:Primary airway epithelial cells were isolated from WT and Club LRP1-/- mice as in Oreffo et al (Isolation of Clara cells from the mouse lung. Environmental health perspectives. 1990;85:51-64). Briefly, mice were anesthetized with isofluorane and their trachea was cannulated. Abdominal cavity was opened, and heart was perfused with PBS until the lungs and liver were free of blood. The lungs were then lavaged through the tracheal cannula with 1 mL saline, followed by protease solution (0.25% crystalline trypsin in 133 mM NaCl, 5.2 mM KCl, 1.89 mM CaCl2, 1.29 mM MgSO4, 2.59 mM phosphate buffer, pH 7.4, 10.3 mM Hepes buffer , pH 7.4, glucose 1 mg/ml), and then infused with protease solution according to the standard lung perfusion guidelines by the American Thoracic Society (61). Lungs were maintained filled with protease solution at 37 C for 15 min. Then, lungs and airways were extracted from the chest cavity and dissected in protease solution supplemented with fetal bovine serum. Trachea and major bronchi were removed and the parenchyma was diced in small pieces, placed in solution B (5.2 mM KCl, 2.59 mM phosphate buffer, pH 7.4, 10.3 mM Hepes buffer, Ph 7.4, glucose 1 mg/ml) and manually shaken to release the digested cells. The cell suspension was then filtered through gauze and 100 and 40 um mesh. The primary cell digest was centrifuged twice at 32 x g for 6 min at 10 C in 4 mL solution B with 250 ug/mL DNAse and the final pellet collected.
For proteomic analysis. Airway epithelial cells collected as above were submitted to Bioproximity LLC (Chantilly, VA, USA). For proteome profiling, cells were trypsinized and equal amounts of protein per sample were used for UPLC-MS/MS for identification of protein IDs.
2018-11-26 | MSV000083163 | MassIVE