COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors
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PROVIDER: PRJNA975121 | ENA |
REPOSITORIES: ENA
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Project description:COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors
| PRJNA860578 | 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:We characterized primary human bronchial epithelial cells (pHBECs) from end-stage COPD and pulmonary healthy individuals. The transcriptomic profiles were assessed by single cell analysis in serial samples of pHBEC culture focussing on basal cell differentiation.
2024-04-01 | GSE233145 | 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:Background: Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process is unknown Results: The objective of this study was to define the role of the Notch ligand JAG1 in regulating BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. Conclusions: These data demonstrate JAG1 mediated Notch signaling regulates differentiation of BC into secretory cells. This study demonstrates that expression of the Notch ligand JAG1 is highly enriched in basal stem/progenitor cells (BC) of the human airway epithelium and that modulation of its expression levels during differentiation of BC play an important role in regulating secretory cell differentiation with no effect on ciliated cell differentiation. These observations have implications for developing novel targets to specifically modulate levels of secretory cells in human airway disorders.
2017-08-23 | GSE76421 | GEO
Project description:Transcriptional profiling of ciliating mouse tracheal epithelial cells compared to non-ciliating cells at two timepoints, ALI+4 and ALI+12, during differentiation in vitro. These cells are obtained from a transgenic mouse expressing GFP from a human FOXJ1 promoter, so that cells destined to become ciliated can be sorted by FACS based on their expression of GFP. Likewise, the control non-ciliated cells are identified by their lack of GFP expression. Ciliated cells were compared to Universal Reference RNA, and non-ciliated cells were compared to Universal Reference RNA. Two-color arrays were used to compare non-ciliated cells, or ciliated cell samples taken at 4 days or 12 days after establishment of the air-liquid interface (ALI), to a Universal Reference RNA. Ciliated cells vs. Universal Reference RNA or Non-ciliated cells vs. Universal Reference RNA. 3 biological replicates from independently grown and harvested cell cultures were performed for non-ciliated cells, 5 biological replicates were performed for a ciliated cell samples at ALI+12, and 3 biological replicates plus 2 technical replicates were performed for ciliated cell samples at ALI+4.
2012-11-29 | E-GEOD-42500 | 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:To identify key genes that define surface airway epithelial (SAE) basal cells, we FACS isolated basal, ciliated, and club cell populations as previously reported (Zhao et al., 2014; PMID: 25043474) and performed microarray analysis on isolated mRNA. For fractionating SAE into basal, club, and ciliated populations, cells were stained with EpCAM-PECy7 (eBiosciences), GSIβ4-FITC (Sigma), SSEA1-Alexa Fluor® 647 (BioLegend), and CD24-PE (BD Pharmingen) for 30 minutes on ice as previously described (Zhao et al., 2014), prior to FACS. Basal cells were considered EpCAM+ and GSIβ4+. Secretory cells were considered EpCAM+ and SSEA1+. Ciliated cells were considered EpCAM+, GSIβ4- and CD24+. Primary SAE cells were harvested from C57BL/6 mice and sorted into basal, ciliated, and club cell populations for the purpose of identifying enrichment of transcripts specific to each cell type population.
2018-04-30 | GSE111557 | GEO
Project description:Epidermis of Xenopus embryos forms a mucociliary epithelium constituted of basal, scattered, secreting and ciliated cells and is histologically similar to human airway mucociliary epithelium. We compared microRNAs signatures of epidermis of Xenopus embryos at stage 11.5 (gastrula, non ciliated epidermis) and at stage 26 (tailbud, ciliated epidermis). 2 technical replicates of a pool of 50 explants for each stage 11.5 (non ciliated) and 26 (ciliated) of Xenopus laevis development
2011-06-06 | E-GEOD-22146 | biostudies-arrayexpress
Project description:Transcriptional profiling of ciliating mouse tracheal epithelial cells compared to non-ciliating cells at two timepoints, ALI+4 and ALI+12, during differentiation in vitro. These cells are obtained from a transgenic mouse expressing GFP from a human FOXJ1 promoter, so that cells destined to become ciliated can be sorted by FACS based on their expression of GFP. Likewise, the control non-ciliated cells are identified by their lack of GFP expression. Ciliated cells were compared to Universal Reference RNA, and non-ciliated cells were compared to Universal Reference RNA.
2012-11-29 | GSE42500 | GEO