The genetic profiles based single cell level in a murine model of pancreatic carcinogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE202004 | GEO | 2022/05/04
REPOSITORIES: GEO
Similar Datasets
Project description:We established cell lines (fibroblasts) from pancreatic tumors in a mouse model of pancreatic carcinogenesis overexpressing METTL3 and performed RNAseq to examine changes in the gene profile of fibroblasts upon METTL3 overexpression. For the present study, we used the database of murine embryonal fibroblast (MEF) as the experimental control (GSE133753; GSM3926647, GSM3926648, GSM3926649 and GSE193354; GSM5795876, GSM5795877, GSM5795878).
2022-05-05 | GSE202113 | GEO
Project description:The genetic profiles based single cell level in a murine model of pancreatic carcinogenesis
| PRJNA834029 | ENA
Project description:Primary murine pancreatic cancer cells (referred to as NKC cells) derived from transgenic mice with pancreas-specific constitutive activation of NFATc1 and KrasG12D mutation in the presence or absence of NFATc1 expression were analyzed for target gene signatures.
2014-06-30 | E-MTAB-1244 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE32676: Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer [mRNA] GSE32678: Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer [miRNA] GSE32682: Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer [SNP] Refer to individual Series
2011-10-07 | E-GEOD-32688 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal malignancies, characterized by aggressive local tumor growth and metastatic spread, in part driven by fibroblast-mediated stromal reactions in the tumor microenvironment. Early detection is critical for improved patient outcomes. In this study, we investigate the molecular cues within fibroblasts that offer promise for early PDAC diagnosis. We employ RNA sequencing of fibroblasts from KPC mouse models at pivotal time points, corresponding to the early preinvasive stages of pancreatic cancer. Our analysis reveals a substantial upregulation of gene sets associated with adipogenesis, fatty acid metabolism, and the ROS pathway in 12-week KPC-fibroblasts, indicative of metabolic reprogramming and redox regulation during early PDAC initiation. We narrow our focus to 26 potential key genes that may facilitate paracrine communication between fibroblasts and preneoplastic cells. Validation of our findings confirms the consistent increase in Angptl4, a gene linked to adipogenesis, and the notable downregulation of Lama2, a crucial extracellular matrix (ECM) gene. This study is the first to observe the elevation of Angptl4 in KPC-fibroblasts, providing essential insights into the role of fibroblasts in early PDAC. Moreover, our results hint at a potential role of fibroblasts in ECM degradation, a process that could support cancer cell proliferation and metastatic invasion. Genes associated with the ECM consistently display downregulation. These discoveries lay the foundation for future investigations into the mechanisms driving fibroblast-mediated elevation of Angptl4 and downregulation of ECM genes and their role in mediating crosstalk between fibroblast and preneoplastic cells. Our investigation into fibroblast transcriptional dynamics during early carcinogenesis offers significant potential for enhancing early diagnostic approaches in combating this deadly malignancy.
2024-12-11 | GSE270121 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality among adults in developed countries. The discovery of the most common genetic alterations as well as the development of organoids models of pancreatic cancer have provided insight into the fundamental pathways driving the progression from normal cell, to non-invasive precursor lesion, to widely metastatic disease, offering new opportunities for the discovery of key activated pathways along cancer progression. Obesity is one of the most serious public health challenges of the 21st century. Several epidemiological studies have shown the positive association between obesity and cancer-related morbidity/mortality, as well as poor prognosis and poorer treatment outcome. Despite strong evidence indicates a link between obesity and cancer incidence, the molecular basis of the initiating events remains largely elusive. This is mainly due to the lack of an accurate and reliable model of pancreatic carcinogenesis that mimics human obesity-associated PDAC, making data interpretation difficult and often confusing. Here we propose, to our knowledge, the best suitable and manageable preclinical tool, based on next-generation cell culture models, to study the effects of obesity on pancreatic carcinogenesis. Therefore we tracked the effects of obesity on the natural evolution of PDAC in a genetically-defined transplantable model of syngeneic murine pancreatic preneoplastic lesion (mP) and tumor (mT) derived organoids that recapitulates the progression of human disease from early preinvasive lesions to metastatic disease. Our models indicated that both genetic- and diet-induced obesity promoted incidence engraftment rate and growth of both preneoplastic and neoplastic organoids, favoring pancreatic cancer progression and distant metastases dissemination. Our obesity models of carcinogenesis mimic the evolution of human pancreatic cancer pathology, promoting carcinogenesis and concomitant accumulation of a myeloid infiltrate. These changes in cancer immune infiltrate were also associated to a specific pattern of anti-inflammatory Th2 signature. Moreover, gene expression profile analysis revealed a change in gene expression programs that addresses cells to different pancreatic subtypes and stromal conditions. Our results suggest that organoid-derived transplants in obese mice represent a suitable system to study early step of carcinogenesis and support the hypothesis that inflammation induced by obesity stimulates tumor progression and metastatization during pancreatic carcinogenesis.
2020-05-26 | PXD018362 | Pride
Project description:Murine models of pancreatic cancer: KPC
| PRJNA836890 | ENA
Project description:To elucidate whether METTL3 plays a role in colorectal cancer tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of METTL3-KO and wild-type HCT116 cells.
2020-04-13 | GSE130012 | GEO
Project description:Damaged tissues have increased risk of cancer development through poorly understood mechanisms. In the pancreas, tissue damage collaborates with activating mutations in the Kras oncogene to dramatically accelerate the formation of early neoplastic lesions and ultimately pancreatic cancer. By integrating genomics, single-cell chromatin assays and spatiotemporally-controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves large-scale chromatin accessibility changes that contribute to the early dysregulation of genes defining human pancreatic cancer. Among the genes most rapidly activated by tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine IL33, which cooperates with mutant Kras in unleashing the epigenetic remodeling program of early neoplasia and neoplastic transformation in the absence of injury. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene regulatory programs that dictate early neoplastic commitment and provides a molecular framework for understanding the interplay between genetics and environmental cues in cancer initiation.
2020-11-25 | GSE154543 | GEO
Project description:Damaged tissues have increased risk of cancer development through poorly understood mechanisms. In the pancreas, tissue damage collaborates with activating mutations in the Kras oncogene to dramatically accelerate the formation of early neoplastic lesions and ultimately pancreatic cancer. By integrating genomics, single-cell chromatin assays and spatiotemporally-controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves large-scale chromatin accessibility changes that contribute to the early dysregulation of genes defining human pancreatic cancer. Among the genes most rapidly activated by tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine IL33, which cooperates with mutant Kras in unleashing the epigenetic remodeling program of early neoplasia and neoplastic transformation in the absence of injury. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene regulatory programs that dictate early neoplastic commitment and provides a molecular framework for understanding the interplay between genetics and environmental cues in cancer initiation.
2021-07-13 | GSE162367 | GEO