Characterizing senescent lung epithelial cells
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ABSTRACT:
PROVIDER: PRJNA699009 | ENA |
REPOSITORIES: ENA
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Project description:We characterized senescent alveolar epithelial cells in an effort to better understand how these cells contribute to lung remodeling and fibrosis. The transcriptional profiles of several different types of senescent lung epithelial cells was evaluated using various induction methods in order to better understand core characteristics associated with the senescent program in epithelial cells of the lung.
2021-03-08 | GSE166034 | GEO
Project description:Proteome analysis of lung epithelial cells of house dust mite-challenged mice. The cells were isolated from frozen tissue section by LASER microdissection.
2019-08-16 | PXD010792 | JPOST Repository
Project description:Recent publications have implicated senescent alveolar epithelial cells as the cause of lung remodeling and fibrosis. We sought to better understand the heterogeneity in the basal epithelial cell population, especially with regards to characterizing senescent alveolar epithelial cells. The basal cell cultures contain a portion of cells that display a senescent phenotype and stain for a marker of senescence. We also sought to understanding the heterogeneity in the fibroblast population. Primary fibroblast cultures stained with myofibroblast markers show that only a portion of the cells are positive for ACTA2, suggesting that there are at least two distinct populations in this particular cell type. The diversity in this cell type remains uncharacterized at this point.
2021-03-08 | GSE166037 | GEO
Project description:Histone modifications in lung epithelial cells
| PRJNA594274 | ENA
Project description:Accumulation of senescent cells in the tumour microenvironment can drive tumourigenesis in a paracrine manner through the senescence-associated secretory phenotype (SASP). Using a new p16-FDR mouse line, we show that macrophages and endothelial cells are the predominant senescent cell types in murine KRAS-driven lung tumours. Single cell transcriptomics identify a population of tumour-associated macrophages, expressing a unique array of pro-tumourigenic SASP factors and surface proteins, that are also present in normal aged lungs. Genetic or senolytic ablation of senescent cells, and macrophage depletion, result in a significant reduction in tumour burden and increased mouse survival of KRAS-driven lung cancer models. Of translational relevance, we reveal the presence of macrophages with senescent features in human lung premalignant lesions, but not in adenocarcinomas. Together, our results have uncovered a population of senescent macrophages contributing to the initiation and progression of lung cancer, thus opening potential therapeutic avenues and cancer preventative strategies.
2023-06-02 | GSE230054 | GEO
Project description:The accumulation of senescent cells promotes aging, but a molecular mechanism that senescent cells use to evade immune clearance and accumulate remains to be elucidated. Here, we report that p16-positive senescent cells upregulate the immune checkpoint protein programmed death-ligand 1 (PD-L1) to accumulate in aging and chronic inflammation. p16-mediated inhibition of CDK4/6 promotes PD-L1 stability in senescent cells via the downregulation of ubiquitin-dependent degradation. p16 expression in infiltrating macrophages induces an immunosuppressive environment that can contribute to an increased burden of senescent cells. Treatment with immunostimulatory anti-PD-L1 antibody enhances the cytotoxic T cell activity and leads to the elimination of p16, PD-L1-positive cells. Our study uncovers a molecular mechanism of p16-dependent regulation of PD-L1 protein stability in senescent cells and reveals the potential of PD-L1 as a target for treating senescence-mediated age-associated diseases.
2024-02-14 | GSE225286 | GEO
Project description:Understanding the important role of the tumour microenvironment on tumour initiation and progression is vital for a comprehensive understanding of cancer biology to design effective treatment strategies. Cellular senescence, while traditionally thought of as a cell autonomous tumour-suppressive response to potentially oncogenic insults, is now appreciated to have paracrine tumour promoting roles. We demonstrate a pro-tumourigenic effect of senescent microenvironmental cells on mouse lung tumour progression. To better understand the characteristics of these pro-tumourigenic senescent cells in the tumour microenvironment, we compare putatively senescent cells (reported by mCherry-expression) and non-senescent cells (mCherry-negative cells) from the lung microenvironment of mice induced to form lung tumours by oncogenic KrasG12D-expression in the lung epithelium. Putatively senescent cells are isolated by FACS, based on mCherry-expression which is expressed under the control of the Cdkn2a (p16) locus using a novel genetically engineered allele (p16FDR/+), along with their non-senescent counterparts for comparison by single cell RNA-sequencing.
2023-06-14 | GSE203447 | GEO
Project description:Three groups of cells, including the control group, the senescent cells group, and the DMC-treated senescent cells group
2023-11-23 | PXD047192 | iProX
Project description:Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease.
2019-01-08 | PXD007180 | Pride
Project description:Molecular mapping of interstitial lung disease reveals a phenotypically distinct senescent basal epithelial cell population
| PRJNA699153 | ENA