Alveolar basal cells differentiate towards secretory epithelial and aberrant basaloid cells in vitro
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ABSTRACT:
PROVIDER: PRJNA813874 | ENA |
REPOSITORIES: ENA
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Project description:We performed a single-cell transcriptome analysis of alveolar basal cells from peripheral lung tissue of patients with idiopathic pulmonary fibrosis (IPF), cultured in DMEM or Cnt-PR-A growth medium.
2022-06-15 | GSE198153 | GEO
Project description:Rationale: Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. Objectives: To elucidate the role of EMT in the development of aberrant basaloid cells from human bronchial epithelium by mapping EMT-induced transcriptional changes at the population and single-cell level. Methods: Human bronchial epithelial cells (HBECs) grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Measurements and Main Results: Comparison of submerged and ALI cultures revealed differential expression of 9,868—protein coding (PC) and long non-coding RNA (lncRNA)—genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,927—PC and lncRNA—genes. While there was no evidence for fibroblast/myofibroblast conversion, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. Conclusions: The substantial transcriptional differences between submerged and ALI cultures highlights that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and a data visualization package for further exploration for potential roles in the lung epithelium in health and lung disease.
2022-04-21 | GSE193682 | GEO
Project description:Rationale: Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. Objectives: To elucidate the role of EMT in the development of aberrant basaloid cells from human bronchial epithelium by mapping EMT-induced transcriptional changes at the population and single-cell level. Methods: Human bronchial epithelial cells (HBECs) grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Measurements and Main Results: Comparison of submerged and ALI cultures revealed differential expression of 9,868—protein coding (PC) and long non-coding RNA (lncRNA)—genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,927—PC and lncRNA—genes. While there was no evidence for fibroblast/myofibroblast conversion, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. Conclusions: The substantial transcriptional differences between submerged and ALI cultures highlights that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and a data visualization package for further exploration for potential roles in the lung epithelium in health and lung disease.
2022-04-21 | GSE193683 | GEO
Project description:Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro
| PRJNA797240 | ENA
Project description:Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro [scRNA-seq]
| PRJNA797244 | ENA
Project description:Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro [bulkRNA-seq]
| PRJNA797245 | ENA
Project description:Introduction: Environmental pollutants irritate and injure the bronchial elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterized. Methods: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBEC) from end-stage COPD, early disease and pulmonary healthy individuals. After nanoparticle exposure of pHBECs at the air liquid interface, cell cultures were characterized by functional assays as well as transcriptome and protein analysis, complemented by single cell analysis in serial samples of pHBEC culture focussing on basal cell differentiation. Results: In end-stage COPD, environmentally abundant doses of zinc oxide nanoparticles (ZnO) aggravated a pro-secretory phenotype at the expense of the multi-ciliated epithelium alongside a reduction of barrier integrity and increased resilience towards cell damage. Similar effects on cellular composition and function were induced by co-treatment of early stage COPD pHEBC cultures with cigarette smoke extract. Time-resolved single cell transcriptomics revealed a unique end stage COPD associated basal cell state characterized by altered Wnt and Notch pathway activation. A conserved set of COPD specific genes persisted from this disease associated basal cell state into its differentiated progeny. Conclusion: We identified COPD stage specific gene program alterations in basal stem cells that affect the cellular composition of the bronchial elevator and may control epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment or prevention strategies.
2024-01-06 | GSE208662 | GEO
Project description:Airway basal cells (BC) function as progenitor cells capable of differentiating into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. The objective of this study was to define the role of Notch signaling in regulating human airway BC differentiation into a pseudostratified mucociliated epithelium. Notch inhibition with γ-secretase inhibitors demonstrated Notch activation is essential for BC differentiation into secre-tory cells and ciliated cells, but more so for the secretory lineage. Sustained Notch activation via lentivirus expression of the intracellular domain of each Notch receptor (NICD1-4) demonstrated that the Notch 2 and 4 pathways have little effect on BC differentiation, while activation of the Notch1 or 3 pathways has a major influence, with persistent expression of NICD1 or 3 resulting in a skewing toward secretory cell differentiation with a parallel decrease in ciliated cell differentiation. These observations provide insights into the control of the balance of BC differentiation into the secretory vs ciliated cell lineage, a balance that is critical for maintaining the normal function of the airway epithelium in barrier defense against the inhaled environment. Array-based expression profiling of the Notch signaling pathway genes specifically in human airway basal cells.
2015-04-13 | E-GEOD-53537 | biostudies-arrayexpress
Project description:Airway basal cells (BC) function as progenitor cells capable of differentiating into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. The objective of this study was to define the role of Notch signaling in regulating human airway BC differentiation into a pseudostratified mucociliated epithelium. Notch inhibition with γ-secretase inhibitors demonstrated Notch activation is essential for BC differentiation into secre-tory cells and ciliated cells, but more so for the secretory lineage. Sustained Notch activation via lentivirus expression of the intracellular domain of each Notch receptor (NICD1-4) demonstrated that the Notch 2 and 4 pathways have little effect on BC differentiation, while activation of the Notch1 or 3 pathways has a major influence, with persistent expression of NICD1 or 3 resulting in a skewing toward secretory cell differentiation with a parallel decrease in ciliated cell differentiation. These observations provide insights into the control of the balance of BC differentiation into the secretory vs ciliated cell lineage, a balance that is critical for maintaining the normal function of the airway epithelium in barrier defense against the inhaled environment.
2015-04-13 | GSE53537 | GEO
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. Goals: Creb3L1 is the closest related human orthologue of Drosophila CrebA. CrebA is required to upregulate genes encoding the protein machinery and cargo in specialized secretory cells. To determine if the human orthologues of CrebA, Creb3L1 and Creb3L2, perform the same function, we expressed the truncated active form of Creb3L1 in non-secretory HeLa cells. We then performed microarray experiments and found that active Creb3L1 is sufficient to upregulate genes encoding the protein machinery of the secretory pathway, as observed with Drosophila CrebA. HeLa cells were transiently co-transfected with truncated Creb3L1 (Creb3L1 T) and GFP. Following 20 hours in culture, GFP positive cells were isolated by FACS and RNA was extracted using the Rneasy kit (Qiagen). As a control, mock transfected cells were also subjected to cell sorting and RNA was extracted using the same protocols. At least three replicates were obtained for each group.
2010-10-18 | E-GEOD-23334 | biostudies-arrayexpress