Cellular response to hypoxia on human bronchial epithelial culture [scRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227508 | GEO | 2023/08/22
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: To identify the cell types change and gene expression change under hypoxia on HBE cells. Methods: The primary human bronchial epithelial cells (HBE) were cultured on air-liquid interface (ALI) conditions. After 4 weeks, the cells were cultured under normoxic, symmetrical hypoxic (3.5% O2), or asymmetrical hypoxic (3.5% O2 basolateral with apical cap ~ 1% O2) conditions for 5 days. The cells were dissociated with Accutase solution and proceeded to scRNA-seq. Results: Asymmetrical hypoxic cells showed more hypoxia-related responses than symmetrical hypoxic cells.
2023-08-22 | GSE227586 | GEO
Project description:Purpose: To identify the gene expression change under hypoxia on HBE cells. Methods: bulk RNA-seq was performed on primary human bronchial epithelial cells (HBE) that were cultured on air-liquid interface (ALI) condition and treated under normoxia or hypoxia (1% O2) for 6hr, 24hr, and 5days. Results: hypoxia-related genes were significantly upregulated under hypoxia including EGLN3.
2023-08-22 | GSE227502 | GEO
Project description:Purpose: To identify the gene expression change under chronic hypoxia on HBE cells. Methods: bulk RNA-seq was performed on primary human bronchial epithelial cells (HBE) that were cultured on air-liquid interface (ALI) condition and treated under normoxia or hypoxia (1% O2) for 5days. Results: inflammatory cytokines, collagen degradation, and angiogenic genes were upregulated under chronic hypoxia.
2023-08-22 | GSE227501 | GEO
Project description:The availability of robust protocols to differentiate induced pluripotent stem cells (iPSCs) into many human cell lineages has transformed research into the origins of human disease. The efficacy of differentiating iPSCs into specific cellular models is influenced by many factors including both intrinsic and extrinsic features. Among the most challenging models is the generation of human bronchial epithelium at air-liquid interface (HBE-ALI), which is the gold standard for many studies of respiratory diseases including cystic fibrosis. Here we perform open chromatin mapping by ATAC-seq and transcriptomics by RNA-seq in parallel, to define the functional genomics of key stages of the iPSC to HBE-ALI differentiation. Within open chromatin peaks the overrepresented motifs include the architectural protein CTCF at all stages, while motifs for the FOXA and GATA pioneer factors families are only seen at early stages, and those regulating key airway epithelial functions, such as EHF, are limited to later stages. The RNA-seq data illustrate dynamic pathways during the iPSC to HBE-ALI differentiation, and also the marked functional divergence of different iPSC lines at the ALI stages of differentiation. Moreover, a comparison of iPSC-derived and lung donor-derived HBE-ALI cultures reveals substantial differences between these models.
2021-01-06 | GSE136858 | GEO
Project description:The availability of robust protocols to differentiate induced pluripotent stem cells (iPSCs) into many human cell lineages has transformed research into the origins of human disease. The efficacy of differentiating iPSCs into specific cellular models is influenced by many factors including both intrinsic and extrinsic features. Among the most challenging models is the generation of human bronchial epithelium at air-liquid interface (HBE-ALI), which is the gold standard for many studies of respiratory diseases including cystic fibrosis. Here we perform open chromatin mapping by ATAC-seq and transcriptomics by RNA-seq in parallel, to define the functional genomics of key stages of the definitive endoderm (DE) to HBE-ALI differentiation. Within open chromatin peaks the overrepresented motifs include the architectural protein CTCF at all stages, while motifs for the FOXA and GATA pioneer factors families are only seen at early stages, and those regulating key airway epithelial functions such as EHF are limited to later stages. The RNA seq data illustrate dynamic pathways during the DE to HBE-ALI differentiation and also the marked functional divergence of different iPSC lines at the ALI stages of differentiation. Moreover, a comparison of iPSC-derived and lung donor-derived HBE cultures reveals substantial differences in these culture models.
2021-01-06 | GSE136857 | GEO
Project description:Acute lung injury (ALI) refers to a clinical syndrome characterized by bilateral lung injury, severe lung diffuse failure and hypoxemia caused by non-cardiogenic pulmonary edema.Sepsis is the leading etiology of ALI and a common admission to the intensive care unit, which induces pulmonary inflammation leading disruption of endothelial-epithelial barriers by surge release of pro-inflammatory cytokines that increases the permeability of the alveolar-capillary membrane, pulmonary infiltration, and edema.Ultimately, gas exchange across the alveolar-capillary membrane is severely impaired and acute respiratory failure and hypoxia occur. ALI patients may suffer from pulmonary inflammation and hypoxia simultaneously or sequentially, those two pathophysiological processes may interact mutually and contribute together to the development of ALI. LPS is the most important biological mediator of sepsis induce secretion of inflammatory cytokines including TNF-α, IL-1, and IL-6 from many cell types in response to bacterial toxins. Thus LPS has been commonly used to establish inflammatory ALI models of rats and mice. Clinically, hypoxia commonly coexists with sepsis; however, the role of hypoxia on the development of inflammatory ALI is unclear. The understanding of interaction of hypoxia and inflammation in ALI is of the importance for the treatment of ALI.
2018-08-21 | GSE111241 | GEO
Project description:Rationale:Cultured human bronchial epithelia (HBE) are the gold standard model for assessing the efficacy of small molecule therapies in cystic fibrosis (CF). However, these cells are difficult to access, especially in young children. Human nasal epithelia (HNE) are used as a surrogate model although it is unknown whether HNE recapitulate the gene expression properties of HBE Objective: To investigate the similarities and differences in gene expression genome-wide between HBE and HNE with a focus on CF lung disease modifier genes. Methods: RNA-sequencing was conducted on paired cultured and naïve HNE and HBE (n=71 samples) collected from 21 patients with CF who underwent lung transplantation. Gene expression was first compared across cultured and naïve samples to assess the impact of the culturing process, then compared between cultured HNE and HBE. Co-expression relationships of CF modifier genes were compared between cultured HNE and HBE. Results: The culturing process had little impact on the expression level of CF lung disease modifier genes. These genes also showed significant equivalent expression between cultured HNE and HBE. Their co-expression relationships in cultured HNE and HBE overlapped significantly, suggesting the corresponding biological processes are consistent across the two tissues. Conclusions: CF lung disease modifier genes have similar expression profiles across cultured HNE and HBE. This supports the use of HNE as a surrogate airway model to investigate CF lung disease, modifier genes and enable investigation of CF precision medicine.
2021-11-15 | GSE172232 | GEO
Project description:Human airway epithelial cells cultured in vitro at air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin, and are widely used as a model of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed global gene expression correlated well between ALI cells and brushed cells, but there were some differences. Gene expression patterns mirrored differences in proportions of cell types (ALI have higher percentages of basal cells, brushed cells have higher percentages of ciliated cells), with ALI cells expressing higher levels of basal cell-related genes and brushed cells expressing higher levels of cilia-related genes. Pathway analysis showed ALI cells had increased expression of cell cycle and proliferation genes, while brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells are a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences in the in vitro vs in vivo environments need to be considered. Affymetrix arrays were used to assess the gene expression of large airway cells cultured in vitro at air-liquid interface (12 samples) and large airway epithelial cells obtained by fiberoptic bronchoscopy of 20 healthy nonsmokers. *** Air-liquid interface Samples not provided in this Series. ***
2010-07-07 | E-GEOD-18637 | biostudies-arrayexpress
Project description:Human airway epithelial cells cultured in vitro at air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin, and are widely used as a model of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed global gene expression correlated well between ALI cells and brushed cells, but there were some differences. Gene expression patterns mirrored differences in proportions of cell types (ALI have higher percentages of basal cells, brushed cells have higher percentages of ciliated cells), with ALI cells expressing higher levels of basal cell-related genes and brushed cells expressing higher levels of cilia-related genes. Pathway analysis showed ALI cells had increased expression of cell cycle and proliferation genes, while brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells are a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences in the in vitro vs in vivo environments need to be considered.
2010-07-07 | GSE18637 | GEO
Project description:The human airways are complex structures with important interactions between cells, extracellular matrix proteins and the biomechanical microenvironment. A robust, well-differentiated in vitro culture system that accurately models these interactions would provide a useful tool for studying normal and pathological airway biology. Here, we report the analysis of a physiologically relevant air-liquid interface (ALI) 3D airway ‘organ tissue equivalent’ (OTE) model with three novel features: native pulmonary fibroblasts, solubilized lung extracellular matrix (ECM), and hydrogel substrate with tunable stiffness and porosity. We demonstrate the versatility of the OTE model by evaluating the impact of these features on HBE cell phenotype. Variations of this model were analyzed during 28 days of ALI culture by evaluating epithelial confluence, trans-epithelial resistance (TEER), and epithelial phenotype via multispectral immuno-histochemistry and next-generation sequencing (NGS). Cultures that included both solubilized lung ECM and native pulmonary fibroblasts within the hydrogel substrate formed well differentiated ALI cultures that maintained a barrier function and expressed similar levels of goblet, club and ciliated markers to native airway tissue. Modulation of hydrogel stiffness did not negatively impact HBE differentiation and could be a valuable variable to alter epithelial phenotype. This study highlights the capability and versatility of a 3D airway OTE model to model the multiple components of the human airway 3D microenvironment.
2022-07-14 | GSE207931 | GEO