Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA391186 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In order to compare the gene expression profile of acinar-to-ductal metaplasia (ADM), ductal and acinar cells in the setting of pancreatitis, which were obtained by laser-capture microdissection (LMD) from frozen sections of wild type mice pancreata 2 days after caerulein administration, we performed microarray analysis. ADM has an intermediate property between ductal and acinar cells in the setting of pancreatitis, and Cxcr4 mRNA which is expressed in multipotent pancreatic progenitors, were up-regulated in ADM compared with ductal cells or acinar cells. Notably, in consistent with our immunostaining data, Dclk1 mRNA was highly expressed in ADM cells compared with ductal and acinar cells.
2017-06-21 | GSE100270 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDA) is the devastating disease in urgent need to identify new strategies for diagnosing and treating. Chronic pancreatitis is a risk factor for PDA in humans. Nardilysin (Nrdc, NRDC), a zinc peptidase of the M16 family has been shown to promote cancer cell growth in vitro. Here, we report that pancreatic deletion of Nrdc dramatically accelerates formation of pancreatic intraepithelial neoplasia (PanIN) and invasive PDA in the presence of oncogenic Kras. Nrdc was expressed in the nucleus of pancreatic acinar cells and pancreatic deletion of Nrdc was dispensable for pancreatic development in mice, but led to spontaneous chronic pancreatitis concomitant with acinar-to-ductal conversion, fibrotic change, infiltrated inflammatory cells, increased apoptosis, and atrophic pancreas in adult mice. Ex vivo acinar cell explants culture experiments showed that acinar-to-ductal conversion was not induced through a cell autonomous mechanism and that expression of several chemokines, including Cxcl10, was markedly up-regulated in Nrdc-null pancreatic acinar cells. Microarray analysis revealed that pathways implicated in pancreatitis and tumorigenesis, including chemotaxis, NF-κB and Erk1/2 signaling, were up-regulated in Nrdc-cKO pancreata compared with WT controls. Finally, immunostaining for NRDC revealed absence of NRDC expression in a subset of human PanINs and PDAs. These data demonstrate a previously unappreciated tumor suppressive function of Nrdc in the pancreas through suppressing chronic pancreatitis with acinar-to-ductal conversion in mice.
2017-05-31 | GSE99438 | GEO
Project description:Pancreatitis is triggered by environmental or cellular stress and is the leading contributor to pancreatic ductal adenocarcinoma. Altered gene expression in response to acinar cell stress determines the severity and duration of pancreatitis. However, it is unclear what factors contribute to this phenomenon. Here, we define a novel role for Activating Transcription Factor 3 (ATF3) during pancreatic injury. ATF3, a key mediator in the unfolded protein response, is robustly expressed in acinar cells during pancreatitis. Targeted deletion of Atf3 altered the molecular response to injury, with Atf3-/- acinar cells maintaining cell organization in response to cerulein, a well-established inducer of pancreatitis. Characterization of the mechanism using chromatin immunoprecipitation followed by Next Generation sequencing (ChIP-seq) identified 11,771 enrichment spots for ATF3, with known transcriptional start sites for >3,000 genes within 5 kb of ATF3 enrichment. Gene ontology analysis revealed a significant representation of ATF3 enrichment to genes affecting cell organization, including Mist1, a molecule required for establishing acinar cell organization. We confirmed a direct interaction of ATF3 to the Mist1 promoter during pancreatitis, and showed that ATF3 is required for altered Mist1 expression in response to injury. Finally, we demonstrate that ATF3 repression of Mist1 involves HDAC5. These findings suggest that ATF3 is a key transcriptional regulator during pancreatitis and promotes loss of the mature acinar cell phenotype in response to pancreatic injury. Two samples were produced from male mice 4 hours after CIP initiation from intraparitoneal injections of cerulein, a ChIP sample using an ATF3 antibody and an IP control.
2015-08-01 | E-GEOD-60250 | biostudies-arrayexpress
Project description:To investigate the underlying changes during acinar-to-ductal metaplasia induced by different oncogenes and by acute pancreatitis, pancreatic tissue was isolated from 10 week old control wt, KrasG12D, Pi3kCAH1047R and Mek1dd mice and from mice of the same genotypes after induction of acute pancreatitis.
2024-04-06 | E-MTAB-13946 | biostudies-arrayexpress
Project description:Pancreatitis is triggered by environmental or cellular stress and is the leading contributor to pancreatic ductal adenocarcinoma. Altered gene expression in response to acinar cell stress determines the severity and duration of pancreatitis. However, it is unclear what factors contribute to this phenomenon. Here, we define a novel role for Activating Transcription Factor 3 (ATF3) during pancreatic injury. ATF3, a key mediator in the unfolded protein response, is robustly expressed in acinar cells during pancreatitis. Targeted deletion of Atf3 altered the molecular response to injury, with Atf3-/- acinar cells maintaining cell organization in response to cerulein, a well-established inducer of pancreatitis. Characterization of the mechanism using chromatin immunoprecipitation followed by Next Generation sequencing (ChIP-seq) identified 11,771 enrichment spots for ATF3, with known transcriptional start sites for >3,000 genes within 5 kb of ATF3 enrichment. Gene ontology analysis revealed a significant representation of ATF3 enrichment to genes affecting cell organization, including Mist1, a molecule required for establishing acinar cell organization. We confirmed a direct interaction of ATF3 to the Mist1 promoter during pancreatitis, and showed that ATF3 is required for altered Mist1 expression in response to injury. Finally, we demonstrate that ATF3 repression of Mist1 involves HDAC5. These findings suggest that ATF3 is a key transcriptional regulator during pancreatitis and promotes loss of the mature acinar cell phenotype in response to pancreatic injury.
2015-08-01 | GSE60250 | GEO
Project description:Global microRNA expression profiling of microdissected pancreatic tissues were collected using Agilent miRNA microarrays (G4470B, Sanger 10.1) carrying 723 individual human miRNA probes. Four different sources of RNA were analyzed: microdissected normal pancreatic ductal cells (ND, n=4),microdissected acinar cells (AC, n=4), macrodissected chronic pancreatitis (CP, n=5) and micordissected xenograft tissues derived from primary pancreatic ductal adenocarcinomas (PDAC, n=5). Four condition (AZ, ND, PDAC, CP), each condition is represented by 4 to 5 biological replicates
2011-09-28 | E-GEOD-25820 | biostudies-arrayexpress
Project description:Although early developmental processes involve cell fate decisions that define the body axes and establish progenitor cell pools, development does not cease once cells are specified. Instead, most cells undergo specific maturation events where changes in the cell transcriptome ensure that the proper gene products are expressed to carry out unique physiological functions. Pancreatic acinar cells mature post-natally to handle an extensive protein synthetic load, establsih organized apical-basal polarity for zymogen granule trafficking, and assemble gap-junctions to perimt efficient cell-cell communication. Despite significant progress in defining transcriptional networks that control initial acinar cell specification and differentiation decisions, little is know regarding the role of transcription factors in the specification and maintenance of maturation events. One candidate maturation effector is MIST1, a secretory cell-restricted transcription factor that has been implicated in controlling regulated exocytosis events in a number of cell types. Embryonic knock-out of MIST1 generates acinar cells that fail to establish an apical-basal organization, fail to properly localize zymogen granule and fail to communicate intra-cellularly, making the exocrine organ highly suceptible to pancreatic diseases. In an effort to identify the gene expression differences responsible for MIST1 regulating mature acinar properties. We generated a tamoxifen-inducible mouse model where MIST1 expression could be activated in vivoand performed gene expression arrays on wildtype, MIST1-null, and induced MIST1 pancreatic RNA.
2012-05-04 | GSE34232 | GEO
Project description:Background & Aims: Perturbations in pancreatic ductal bicarbonate secretion often result in chronic pancreatitis. Although the physiological mechanism of ductal secretion is known, its transcriptional control is not well characterized. Here, we investigate the role of the transcription factor Hematopoietically-expressed homeobox protein (Hhex) in pancreatic secretion and pancreatitis. Methods: We derived mice with pancreas-specific, Cre-mediated Hhex gene ablation to determine the requirement of Hhex in the pancreatic duct in early life and in adult stages. Histological and immunostaining analyses were used to detect the presence of pathology. Pancreatic primary ductal cells (PDCs) were isolated to discover differentially expressed transcripts upon acute Hhex ablation. Results: Hhex protein was detected throughout the embryonic and adult ductal trees. Ablation of Hhex in pancreatic progenitors resulted in postnatal ductal ectasia associated with acinar-to-ductal metaplasia, a progressive phenotype that ultimately resulted in chronic pancreatitis. Hhex ablation in adult mice, however, did not cause any detectable pathology. Ductal ectasia did not result from perturbations in primary cilia, but was consistent with the effects of primary ductal hypertension. RNA-seq analysis of Hhex-ablated PDCs indicated the G-protein coupled receptor Natriuretic peptide receptor 3, implicated in paracrine signaling, was upregulated 4.70-fold. Conclusions: Although Hhex is dispensable for adult pancreatic function, ablation of Hhex in pancreatic progenitors results in profound pancreatitis that is consistent with primary ductal hypertension. Our data highlight the critical role of paracrine signaling in maintaining ductal homeostasis, especially in early life, and support ductal hypersecretion as a novel etiology of pediatric chronic pancreatitis. Pancreatic primary ductal cells (PDCs) were isolated from uninduced adult HhexL/L;Sox9CreERT2 (n=2) and littermate control HhexL/L (n=2) mice. PDCs were treated with 500nM 4-hydroxytamoxifen in vitro for 4 days, and then RNA was collected for transcriptome analysis.
2015-11-20 | E-GEOD-63526 | biostudies-arrayexpress
Project description:Expression profiles of Brg1-depleted acinar cells during ductal conversion
| PRJNA361287 | ENA
Project description:The exocrine compartment of the pancreas consisting of ducts and acini makes up most of the pancreatic tissue and is the site of origin for pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Our understanding of the initiation and progression of human PDAC is limited because of challenges associated with maintaining acinar cells in culture. Here we report the commitment of human pluripotent stem cells towards pancreatic duct-like and acini-like organoids that express properties of the neonatal exocrine pancreas. The expression of PDAC-oncogenes KRasG12D or GNASR201C induced cell lineage-specific effects where GNASR201C was more effective in ductal compared to acinar organoids. KRasG12D was more effective in modeling cancer in vivo when expressed in acinar cells and was associated with acinar to ductal metaplastic changes in culture and in vivo. Thus we demonstrate lineage tropism and plasticity in the human exocrine pancreas and identify a renewable source of ductal and acinar epithelia for understanding exocrine development and diseases.
2021-04-16 | GSE169008 | GEO