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COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors

ABSTRACT: COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors

PROVIDER: PRJNA860578 | ENA |

REPOSITORIES: ENA

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COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors

Project description:COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors

| PRJNA975121 | ENA

COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors

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

COPD basal cells are primed towards secretory to multi-ciliated cell imbalance driving increased resilience to environmental stressors

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

Stress resilience is established during development and is regulated by complement factors

Project description:Individuals in a population respond differently to stressful situations. While resilient individuals recover efficiently, others are susceptible to the same stressors. Most existing information regarding the factors regulating stress resilience in vertebrates is from specific areas of the brain from adult rodents or humans. In order to study resilience during development, we established a new paradigm to identify resilience in zebrafish larvae. Using this assay, we identified resilient and susceptible subsets of zebrafish larvae at 6 days post fertilization and performed gene expression analysis on whole larvae.

2023-01-05 | GSE193433 | GEO

The Ciliated Cell Transcriptome: Ciliated Mouse Tracheal Epithelial Cells vs Control Non-ciliated Mouse Tracheal Epithelial Cells during in Vitro Differentiation

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

microRNAs signatures of Xenopus laevis embryo epidermis at stage 11 (non ciliated) and 26 (ciliated) using high throughput sequencing

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

The Ciliated Cell Transcriptome: Ciliated Mouse Tracheal Epithelial Cells vs Control Non-ciliated Mouse Tracheal Epithelial Cells during in Vitro Differentiation

2012-11-29 | GSE42500 | GEO

microRNAs signatures of Xenopus laevis embryo epidermis at stage 11 (non ciliated) and 26 (ciliated) using high throughput sequencing

2011-06-07 | GSE22146 | GEO

Hippocampal synaptoproteomic changes of susceptibility and resilience of rats to chronic social isolation

Project description:The susceptibility to chronic social isolation (CSIS) is associated with development of major depression (MD). Recent studies relate MD with altered expression of synaptic proteins in specific brain regions, whereby some individuals exposed to the stressors are resistant to the stress. To explore the neurobiological underpinnings and identify candidate biomarkers for MD, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression. This model generates two stress-response phenotypes, reflecting CSIS-sensitive (depressive-like behaviour) and CSIS-resilience, assessed by sucrose preference test. Our aim was to characterize the synaptoproteome changes representative of potential long-term changes in protein expression underlying susceptibility or resilience to stress.

2020-11-27 | PXD019790 | Pride

The HAPSTR2 retrogene buffers stress signaling and resilience in mammals

Project description:We recently identified HAPSTR1 (C16orf72) as a key component in a novel pathway which regulates the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding. Here, we identify a functional paralog to HAPSTR1: HAPSTR2. HAPSTR2 formed early in mammalian evolution, via genomic integration of a reverse transcribed HAPSTR1 transcript, and has since been preserved under purifying selection. HAPSTR2, expressed primarily in neural and germline tissues and a subset of cancers, retains established biochemical features of HAPSTR1 to achieve two functions. In normal physiology, HAPSTR2 directly interacts with HAPSTR1, markedly augmenting HAPSTR1 protein stability in a manner independent from HAPSTR1's canonical E3 ligase, HUWE1. Alternatively, in the context of HAPSTR1 loss, HAPSTR2 expression is sufficient to buffer stress signaling and resilience. Thus, we discover a mammalian retrogene which safeguards fitness.

2023-01-18 | GSE219209 | GEO

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