Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA349475 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4435980.fastq.gz | Fastqsanger.gz | |||
| SRR4435981.fastq.gz | Fastqsanger.gz | |||
| SRR4435982.fastq.gz | Fastqsanger.gz | |||
| SRR4435983.fastq.gz | Fastqsanger.gz | |||
| SRR4435984.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection.
2017-03-14 | GSE88997 | GEO
Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation. Pancreatic tissue from 4 groups of mice were used in this project: (1) the pancreas normal appearance of Pdx1-cre;KrasLSL-G12D;IKK2/beta mice, (2) the normal pancreas of Pdx1-cre;KrasLSL-G12D mice, (3) the pancreatic lesion of pancreatic intraepithelial neoplasia (PanIN) of Pdx1-cre;KrasLSL-G12D mice, and (4) the pancreatic lesion of PDAC of Pdx1-cre;KrasLSL-G12D mice. Each group included three mice. RNA samples from mouse pancreas were hybridized on GeneChip Mouse Gene 1.0 ST arrays (Affymetrix). Group (1) and group (2) were compared, and group (2), group (3) and group (4) were compared.
2012-01-24 | E-GEOD-33322 | biostudies-arrayexpress
Project description:Pancreatic Ductal Adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells where they undergo “ductal retrogression” to form IPMN-PDA. Brg1, a catalytic subunit of the SWI/SNF complexes, plays a critical antagonistic role in IPMN-PDA development. In mature duct cells Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We have exploited this duality of Brg1 functions to develop a novel therapeutic approach using an epigenetic drug JQ1. In summary, this study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA. Duct cells were isolated from mice of 3 different genotypes and duct cells from 3 mice of each genotype were sequenced. For the put back experiments, control retrovirus and that expressing Brg1 were transdcued in Brg1 null IPMN mouse cell line.
2015-07-29 | E-GEOD-65315 | biostudies-arrayexpress
Project description:The new concept of neoplastic lesion of biliary tree, Biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), as a conunterpart of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN), have been reported to be precancerous lesions in hilar and extrahepatic cholangiocarcinoma and arise from lining bile duct epithelium and peribiliary gland (PBG) under inflammation microenvironment in human. However, mouse model is lacking different from intrahepatic cholangiocarcinoma arised from canal of Hering in the liver. In a Doxycyclin-controlled transgenic mouse model of BilIN and IPNB, overexpression of Fibroblast Growth Factor 10 (FGF10) phenocopies human pathology with mutistep progression of cholangiocarcinogenesis in chronic cholangitis. The development and branching morphogenesis of BilIN and IPNB was induced by Fgf10/Erk signal and inhibited by MEK inhibiter. Pdx1+ PBG cells present in IPNB were able to lineage trace the early IPNB lesion as well as Krt19+ cholangiocytes. BiliN and IPNB with Kras mutation was irreversible different from no Kras mutation, and loss of p16 contributed to malignant transformation of BilIN and IPNB. Our data challenge the common paradigms regarding the pathogenesis of BilIN and IPNB.
2019-11-12 | GSE119227 | GEO
Project description:Pancreatitis is more frequent in type 2 diabetes (T2DM) although the underlying cause is unknown. We tested the hypothesis that ongoing beta-cell stress and apoptosis in T2DM induces ductal tree proliferation, particularly the pancreatic duct gland (PDG) compartment, and thus potentially obstructs exocrine outflow. PDG replication was increased two-fold in human pancreas from individuals with T2DM (P<0.01), and was associated with increased pancreatic intraepithelial neoplasia (PanINs) (P<0.05), lesions associated with pancreatic inflammation and with the potential to obstruct pancreatic outflow. Increased PDG replication (p<0.05) in the prediabetic HIP rat model of T2DM was concordant with increased beta-cell stress but preceding metabolic derangement. Moreover, the most abundantly expressed chemokines released by the islets in response to beta-cell stress in T2DM, CXCL1, 4 and 10, induced proliferation in human pancreatic ductal epithelium (p<0.05). Also, the diabetes medications that are reported as potential modifiers for the risk of pancreatitis in T2DM modulated PDG proliferation accordingly. We conclude that chronic stimulation and proliferation of the PDG compartment of the pancreas in response to islet inflammation in T2DM is a novel mechanism that serves as a link to the increased risk for pancreatitis in T2DM and may potentially be modified by currently available diabetes therapy.
2016-12-02 | GSE90779 | GEO
Project description:Pancreatic Ductal Adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells where they undergo “ductal retrogression” to form IPMN-PDA. Brg1, a catalytic subunit of the SWI/SNF complexes, plays a critical antagonistic role in IPMN-PDA development. In mature duct cells Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We have exploited this duality of Brg1 functions to develop a novel therapeutic approach using an epigenetic drug JQ1. In summary, this study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA.
2015-07-29 | GSE65315 | GEO
Project description:Gene expression data from the RNA sequencing of laser microdissected pancreatic intraepithelial neoplasia and pancreatic normal ducts.
2018-03-17 | GSE96784 | GEO
Project description:Inflammation of the pancreas contributes to the development of diabetes mellitus. Although it is well-accepted that local inflammation leads to a progressive loss of functional beta cell mass that eventually causes the onset of the disease, the development of islet inflammation remains unclear. Here, we used single-cell RNA sequencing to explore the cell type-specific molecular response of primary human pancreatic cells exposed to an inflammatory environment. We identified a duct subpopulation presenting a unique proinflammatory signature among all pancreatic cell types. Overall, the findings of this study point towards a role for duct cells in the propagation of islet inflammation, and in immune cell recruitment and activation, which are key steps in the pathophysiology of diabetes mellitus.
2024-04-10 | GSE263365 | GEO
Project description:Lineage tracing using genetically engineered mouse models has become an essential tool for investigating cell-fate decisions of progenitor cells and biology of mature cell types, with respect to physiology and disease progression. To study disease development, an inventory of an organ’s cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We isolated duct cells within the murine pancreas using the DBA lectin sorting strategy that labels all pancreatic duct cell types. Our data contest the paradigm suggested by previous single cell studies that murine pancreatic duct cells are homogenous. We describe an epithelial mesenchymal transitory axis among our two subpopulations of pancreatic duct cells and identify SPP1 as a regulator of this phenotype and human duct cell de-differentiation. Our results further define functional heterogeneity of pancreatic duct subpopulations by elucidating a role for Geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis.
2021-02-28 | GSE159343 | GEO
Project description:Dclk1 expression defines a rare population of cells in normal pancreas whose frequency is increased at early stages pancreatic tumors. The identity and the precise roles of Dclk1 expressing cells in pancreas are matter of debate, although the concept of their involvement in a number of key functions, including regeneration and neoplasia, has emerged. We employed a novel Dclk1 reporter mouse model and single cell RNAseq analysis to define Dclk1 expressing cells in normal pancreas and pancreatic neoplasia. In normal pancreas, Dclk1 epithelial expression identifies subsets of ductal, islet and acinar cells. In pancreatic neoplasia, Dclk1 expression identifies five epithelial cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells represent the main ones. These cells play opposing roles in pancreatic neoplasia, with Dclk1+ ADM-like cells sustaining tumor growth and Dclk1+ tuft-like cells restraining tumor progression. The differentiation of Kras mutant acinar cells into Dclk1+ tuft-like cells requires the activation of SPIB and is further supported by a cellular loop involving cancer group 2 innate lymphoid cells (ILC2) and activated fibroblasts (CAFs) that provide IL13 and IL33, respectively. In turn, Dclk1+ tuft-like cells release angiotensinogen that play protective roles against pancreatic neoplasia. Overall, our study provides novel insights on the biology of Dclk1+ cells in normal pancreas and also unveils a protective axis against pancreatic neoplasia involving Dclk1+ tuft-like cells, ILC2 and CAFs, which ultimately results in angiotensinogen release.
2024-10-08 | GSE259357 | GEO