Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Investigate the role of Wnt/beta-catenin signaling in development of the exocrine pancreas

ABSTRACT: beta-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of beta-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that beta-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of beta-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of beta-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of beta-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed beta-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis. Keywords: Time course

ORGANISM(S): Mus musculus

PROVIDER: GSE7430 | GEO | 2007/04/04

SECONDARY ACCESSION(S): PRJNA97951

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of mouse pancreas at embryonic days 14.5 and 16.5 from animals lacking beta-catenin, a mediator of Wnt signaling and a component of the cadherin-catenin epithelial adhesion complex

Project description:Beta-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of beta-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that beta-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of beta-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of beta-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of beta-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed beta-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis. Experiment Overall Design: Parameter: embryonic pancreas from wild type and Pdx1Cre/+; beta-cateninflox/flox Experiment Overall Design: Sample type: RNA Experiment Overall Design: Source name: Embryonic day 14.6 and 16.5 pancreas Experiment Overall Design: Organism: Mus Musculus Experiment Overall Design: Strain: Derived from an intercross of Pdx1Cre/+ ; beta-cateninflox/+ mice. Experiment Overall Design: Extracted molecule:Total RNA Experiment Overall Design: In the study, we hybridized RNA from Embryonic day 14.6 and 16.5 pancreas of wild type (WT) control and Pdx1Cre/+; beta-cateninflox/floxÂ beta-catenin null in the pancreas) embryonic pancreas to Affymetrix MOE430 2.0 GeneChip® arrays containing 45,101 well characterized mouse genes/ESTs.

2007-12-13 | E-GEOD-7430 | biostudies-arrayexpress

Gene expression analysis between the pancreatic tissues of Pdx1-cre;Kras LSL-G12D and Pdx-cre;KrasLSL-G12D;IKK2/beta F/F mice

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

A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas

Project description:Pancreatic and duodenal homeobox 1 (PDX1) is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 binding in human or mouse developing pancreas have not been examined. To address this knowledge gap, we performed PDX1 ChIP-seq and single-cell RNA-seq using fetal human pancreata. We integrated our datasets with published datasets and revealed the dynamics of PDX1 binding and potential cell-lineage-specific PDX1 bound genes in the pancreas from fetal to adult stages. We identified a core set of developmentally conserved PDX1 bound genes that reveal the broad multifaceted role of PDX1 in pancreas development. Despite the well-known, dramatic changes in PDX1 function and expression, we found that PDX1 bound genes are largely conserved from embryonic to adult stages. This points towards a dual role of PDX1 in regulating the expression of its targets at different ages, dependent on other functionally-congruent or directly-interacting partners. We also showed that PDX1 binding is largely conserved in mouse pancreas. Together, our study reveals PDX1 targets in the developing pancreas in vivo and provides an essential resource for future studies on pancreas development.

2022-04-25 | GSE201230 | GEO

Pancreas-specific miR-216a regulates proliferation and endocrine and exocrine cell function

Project description:Several miRNAs have tissue-specific patterns consistent with crucial functions in many biological processes and are candidate biomarkers of disease. Yet, there is limited knowledge about the role of pancreas-specific miRNAs in pancreatic pathologies. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. By profiling miRNAs from human islets and subsequent systematic tissue analysis we found that miR-216a is highly enriched in endocrine and exocrine pancreas. Deletion of miR-216a in mice lead to a reduction in islet size, β-cell mass and insulin levels. RNA-sequencing indicated that cell cycle and proliferation were the most significantly regulated biological processes in miR-216 knockout pancreata. miR-216a was induced by TGF-β signalling and inhibition of miR-216a increased apoptosis and decreased cell proliferation in both β- and exocrine cells. Deletion of miR-216a in the pancreatic cancer prone mouse line Kras G12D ;Ptf1a CreER reduced the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels were elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA but also suggests miR-216a as a promising biomarker for diagnosis of pancreatic diseases.

2021-10-22 | GSE159844 | GEO

Pancreas-specific miR-216a regulates proliferation and endocrine and exocrine cell function II

2021-10-22 | GSE159970 | GEO

Identification of Sox9/Pdx1-coregulated Genes During Pancreas Organogenesis

Project description:Sox9/Pdx1 co-regulated target genes were identified by comparing gene expression in Sox9/Pdx1-double heterozygates versus Sox9- or Pdx1- heterozygates pancreata using microarray analysis. Pdx1LacZko (herein designated Pdx1-/+) (Offield et al. 1996) and one Sox9 allele was conditionally deleted in the developing pancreas via recombination of a Sox9-flox allele (Kist et al., 2002) using the Foxa3-Cre transgene (Lee et al., 2005). Total RNA was isolated and pooled from dorsal pancreatic epithelia of e12.5 Sox9fl/+; Foxa3-Cre (Sox9 het), Pdx1-/+ (Pdx1 het) versus Sox9fl/+; Foxa3-Cre; Pdx1-/+ (Sox9/Pdx1 double hets) littermates for three biological replicates

2015-08-07 | E-GEOD-62023 | biostudies-arrayexpress

Identification of Sox9-Regulated Pathways During Early Pancreas Organogenesis

Project description:Sox9 target genes were identified by comparing gene expression in Sox9-ablated versus wild-type pancreata using microarray analysis. Sox9 was conditionally ablated in the developing pancreas via recombination of a Sox9-flox allele (Kist et al., 2002) using the Pdx1-Cre transgene (Gu et al., 2002). Total RNA was isolated and pooled from dorsal pancreatic epithelia of e12.5 Sox9fl/fl; Pdx1-Cre (mutant) versus Sox9fl/fl (wild-type) littermates for three biological replicates.

2012-08-01 | E-GEOD-28669 | biostudies-arrayexpress

Pancreas-specific Sirt1-deficiency in mice compromises beta-cell function without development of hyperglycemia

Project description:Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear.This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1-Cre;Sirt1(ex4F/F) mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1-Cre;Sirt1(ex4F/F) mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2A2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as with a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncover a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted. To uncover other Sirt1-regulated mechanisms, we performed a gene expression microarray analysis comparing pancreata from the 6 month old Sirt1âdeficient mice to their controls (n=3 per group).

2016-03-01 | E-GEOD-67239 | biostudies-arrayexpress

Expression analysis of BMP7 responsive P2RY1/ALK3 expressing progenitor like cells within the human exocrine pancreas

Project description:Purpose: Here we demonstrate ALK3Bright/PDX1+ cells residing within the human pancreatic ducts have progenitor like characteristics. Using flow cytometery, live-cell sorting of ALK3bright/PDX1+ cells is possible using a surrogate surface marker for PDX1 (P2RY1). Treating ALK3bright/P2RY1+ cells with BMP7 results in their expansion. Later removal of BMP7 results in the differentiation of these cells to β-like cells. Here we compare the mRNA expression profiles of these three different cell types (in triplicate). Methods: mRNA profiles of ALK3Bright/P2RY1+ cells isolated from human non-endocrine pancreatic tissue, ALK3Bright/P2RY1+ cells treated with BMP7 and ALK3Bright/P2RY1+ cells differentiated to β-like cells after BMP7 removal were generated by deep sequencing, in triplicate, using Illumina HiSeq PE Cluster Kit v4 and Illumina HiSeq Flow Cell v4 with 50 nt paired end reads plus dual index reads using the Illumina HiSeq SBS kit v4. Sequence reads that passed quality filters were analyzed at the transcript isoform level following alignment using TopHat v2.1.0 followed by exon and gene level counting using Bioconductor easyRNASeq v 2.4.7. Conclusions: Our study represents the first detailed analysis of ALK3Bright/P2RY1+ sorted cells with biological replicates. We demonstrate ALK3Bright/P2RY1+ cells were shown to form progenitor-like epithelial colonies characterized by NKX6.1 and PDX1 expression. Unlike the negative fraction controls, these colonies responded to BMP-7 by generating new β-like cells as well as cells from other pancreatic lineages. The transcriptional profile of these cells and their BMP7 treated counterparts suggest a mitotic and progenitor like state. Our studies confirm the progenitor-like nature of ALK3Bright/PDX1+ cells within the human pancreas and suggest a specific anatomical location within the ductal network.

2018-02-08 | GSE104120 | GEO

TrxG complex catalytic and non-catalytic activity play distinct roles in pancreas progenitor specification and differentiation (E18.5 Dpy30∆P pancreas)

Project description:Purpose: To gain insight into why Dpy30∆P acinar cells fail to express terminal makers, we performed RNA-seq using E18.5 control and Dpy30∆P pancreata. Methods: Floxed Dpy30 mice were crossed to Pdx1-Cre driver mice to obtain conditional deletion of Dpy30 exon 4 in the pancreas. In all studies, knockout mice (Dpy30∆P, Pdx1-Cre; Dpy30flox/flox) were compared to littermate controls (Dpy30flox/flox or Dpy30flox/wt). Results: Differential gene expression analysis demonstrated that endocrine cell hormones such as Ins2 and acinar cell digestive enzymes were downregulated in the E18.5 Dpy30∆P pancreas compared to controls. GO term analysis indicated that genes involved in pancreatic secretion, digestion and proteolysis were reduced in Dpy30∆P cells. Notably, transcripts with very high expression levels (above 9000 FPKM) were more downregulated in the E18.5 Dpy30∆P pancreas compared to transcripts with lower expression levels. Conclusions: Overall, these data suggest increased variation in acinar cell transcript expression in the Dpy30∆P pancreas.

2019-07-12 | GSE134180 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data