Club cells employ regeneration mechanisms during lung tumorigenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA735231 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14736000_1.fastq.gz | Fastqsanger.gz | |||
| SRR14736000_2.fastq.gz | Fastqsanger.gz | |||
| SRR14736200_1.fastq.gz | Fastqsanger.gz | |||
| SRR14736200_2.fastq.gz | Fastqsanger.gz | |||
| SRR14736001_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Club cells employ regeneration mechanisms during lung tumorigenesis
| PRJNA735234 | ENA
Project description:Club cells employ regeneration mechanisms during lung tumorigenesis
| PRJNA735233 | ENA
Project description:Lung adenocarcinoma (LUAD) is one of the deadliest malignancies worldwide. Dynamic lineage changes within the lung epithelium and the high plasticity of these epithelial cells confound the correct identification of the cell-of-origin of LUAD. Here, we combined lineage-tracing mouse models with an autochthonous cell type-independent LUAD model in order to discover the cellular origin of ALK-translocated LUAD. We identified Club and AT2 cells as the cells-of-origin of LUAD. Moreover, we uncovered epigenetic imprints in the tumours originating from Club or AT2 cells by whole-genome bisulfite sequencing. Single-cell transcriptomes of Club cells at different stages of tumour development identified two trajectories of Club cell evolution. On both routes, tumours lose their Club cell identity and gain an AT2-like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
2022-06-30 | GSE176185 | GEO
Project description:Lung adenocarcinoma (LUAD) is one of the deadliest malignancies worldwide. Dynamic lineage changes within the lung epithelium and the high plasticity of these epithelial cells confound the correct identification of the cell-of-origin of LUAD. Here, we combined lineage-tracing mouse models with an autochthonous cell type-independent LUAD model in order to discover the cellular origin of ALK-translocated LUAD. We identified Club and AT2 cells as the cells-of-origin of LUAD. Moreover, we uncovered epigenetic imprints in the tumours originating from Club or AT2 cells by whole-genome bisulfite sequencing. Single-cell transcriptomes of Club cells at different stages of tumour development identified two trajectories of Club cell evolution. On both routes, tumours lose their Club cell identity and gain an AT2-like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
2022-06-30 | GSE176184 | GEO
Project description:The high plasticity of lung epithelial cells, has for many years, confounded the correct identification of the cell-of-origin of lung adenocarcinoma (LUAD), one of the deadliest malignancies worldwide. Here, we employ lineage-tracing mouse models to investigate the cell of origin of Eml4-Alk LUAD, and show that Club and Alveolar type 2 (AT2) cells give rise to tumours. We focus on Club cell originated tumours and find that Club cells experience an epigenetic switch by which they lose their lineage fidelity and gain an AT2-like phenotype after oncogenic transformation. Single-cell transcriptomic analyses identified two trajectories of Club cell evolution which are similar to the ones used during lung regeneration, suggesting that lung epithelial cells leverage on their plasticity and intrinsic regeneration mechanisms to give rise to a tumour. Together, this study highlights the role of Club cells in LUAD initiation, identifies the mechanism of Club cell lineage infidelity, confirms the presence of these features in human tumours, and unveils key mechanisms conferring LUAD heterogeneity.
| S-EPMC9356049 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-30 | GSE176186 | GEO
Project description:Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury.
2017-02-09 | GSE88836 | GEO
Project description:Gene expression patterns of bronchiolar progenitors and club cells in mouse lung were examined by microarray experiments. Although it has not yet been fully characterized, a subset of epithelial cells lining bronchioles are best understood as bronchiolar progenitors that self-renew over the long term and that can differentiate into more differentiated club cells and ciliated cells. The bronchiolar progenitors are distinct from club cells and characteristically express the alveolar type 2 cell marker, prosurfactant protein C, with lower levels of club cell secretory protein/Scgb1a1. There are also functional differences between them; while club cells can be depleted by naphthalene because of the abundance of cytochrome P450 enzyme Cyp2f2, bronchiolar progenitors are resistant to naphthalene-induced depletion because of defects in the enzyme.
2016-02-17 | E-MTAB-4460 | biostudies-arrayexpress
Project description:Tumorigenesis, accompanied by tissue regenerative responses, always occurs during mammalian organ injury. In liver, injury context promotes dedifferentiated liver progenitor-like cells (LPLCs) from hepatocytes for regeneration, and also increases the occurrence of hepatocellular carcinoma (HCC). However, little is known about the contribution of injury specific LPLCs to tumorigenesis. Here, by using lineage tracing model, we have demonstrated that LPLCs are highly susceptible to oncogene-induced tumorigenesis. By using quantitative landscape of differentiation dynamics (LDD) model, we have constructed potential landscape of liver regeneration and tumorigenesis via scRNA-seq data, in order to predict distinct regulations of cell fate decisions. Applying this landscape with in vivo validation by transgenic mouse model, we have found blocking Wnt activation not only inhibits tumorigenesis, but also decreases LPLCs. Surprisingly, by using least action pathway analysis, we have decomposed regeneration and tumorigenesis routes, and found EP300 is specifically involved in tumorigenesis, which is further supported by in vivo EP300-knockout model and EP300 inhibitor assays. These findings might be applied as a framework to find tumor-specific regulators and develop strategies specifically inhibiting tumor initiation while leaving tissue regeneration unaffected.
2024-09-29 | GSE244911 | GEO
Project description:Tumorigenesis, accompanied by tissue regenerative responses, always occurs during mammalian organ injury. In liver, injury context promotes dedifferentiated liver progenitor-like cells (LPLCs) from hepatocytes for regeneration, and also increases the occurrence of hepatocellular carcinoma (HCC). However, little is known about the contribution of injury specific LPLCs to tumorigenesis. Here, by using lineage tracing model, we have demonstrated that LPLCs are highly susceptible to oncogene-induced tumorigenesis. By using quantitative landscape of differentiation dynamics (LDD) model, we have constructed potential landscape of liver regeneration and tumorigenesis via scRNA-seq data, in order to predict distinct regulations of cell fate decisions. Applying this landscape with in vivo validation by transgenic mouse model, we have found blocking Wnt activation not only inhibits tumorigenesis, but also decreases LPLCs. Surprisingly, by using least action pathway analysis, we have decomposed regeneration and tumorigenesis routes, and found EP300 is specifically involved in tumorigenesis, which is further supported by in vivo EP300-knockout model and EP300 inhibitor assays. These findings might be applied as a framework to find tumor-specific regulators and develop strategies specifically inhibiting tumor initiation while leaving tissue regeneration unaffected.
2024-09-29 | GSE244910 | GEO