E-GEOD-55078
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA238470PRJNA238469PRJNA238471
PROVIDER: E-GEOD-55078 | ExpressionAtlas | 2015-08-04
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Nr4a1 and Nr4a3 upregulate cell cycle genes upregulated in the Nkx6.1 β-cell proliferation pathway
| PRJNA238471 | ENA
Project description:Diabetes mellitus is a complex and heterogeneous disease that has β cell dysfunction at its core. Glucose toxicity affects pancreatic islets where it leads to β cell apoptosis. However, the role of JNK/β-catenin signaling pathway in glucotoxic β-cell apoptosis is poorly understood. To identify the potential genes whose expression changed in response to high glucose, we performed microarray analysis of gene expression in the RNAKT-15 cells for 48 h. Among the 41,000 genes tested, 1394 and 741 were twofold-upregulated and -downregulated, respectively. Genes involved in carbohydrate metabolism, cell cycle control, apoptotic process, and response to reactive oxygen species were upregulated. In contrast, genes involved in intracellular protein traffic, cell cycle, cell adhesion-mediated signaling, cell cycle control, response to reactive oxygen species, and apoptotic process were downregulated under high glucose-treated RNAKT-15 cells.
2015-12-21 | GSE76189 | GEO
Project description:A small molecule, AT7867, promotes proliferation of human pluripotent stem cell-derived pancreatic progenitor cells (PPCs), yet detailed mechanisms of its proliferative effect were not fully understood. Here, we performed cell-based siRNA screening on a subset of genes to reveal that WNT7B is a growth factor of human PPCs as previously shown in mouse pancreas development. Although recombinant proteins had no in vitro activity, feeder cell lines stably expressing Wnt7a or Wnt7b enhanced PPC proliferation. Further analyses showed that canonical Wnt signaling pathway was not affected by AT7867 treatment as well as Wnt7a and Wnt7b. Knockdown of a non-canonical Wnt pathway component, PKCα, and its downstream substrate, MARCKS, blocked PPC proliferation suggesting a requirement of this pathway. Phosphoproteome analysis revealed that AT7867 inhibited Yin Yang 1 (YY1) phosphorylation at Ser118, which directly or indirectly regulated expression of WNT7B in PPCs. Taken together, non-canonical Wnt signaling mediated by WNT7B plays a critical role for the expansion of human PPC population that is a promising alternative cell source to generate β cells for the cure of diabetes.
2022-03-27 | PXD018222 | JPOST Repository
Project description:A small molecule, AT7867, promotes proliferation of human pluripotent stem cell-derived pancreatic progenitor cells (PPCs), yet detailed mechanisms of its proliferative effect were not fully understood. Here, we performed cell-based siRNA screening on a subset of genes to reveal that WNT7B is a growth factor of human PPCs as previously shown in mouse pancreas development. Although recombinant proteins had no in vitro activity, feeder cell lines stably expressing Wnt7a or Wnt7b enhanced PPC proliferation. Further analyses showed that canonical Wnt signaling pathway was not affected by AT7867 treatment as well as Wnt7a and Wnt7b. Knockdown of a non-canonical Wnt pathway component, PKCα, and its downstream substrate, MARCKS, blocked PPC proliferation suggesting a requirement of this pathway. Phosphoproteome analysis revealed that AT7867 inhibited Yin Yang 1 (YY1) phosphorylation at Ser118, which directly or indirectly regulated expression of WNT7B in PPCs. Taken together, non-canonical Wnt signaling mediated by WNT7B plays a critical role for the expansion of human PPC population that is a promising alternative cell source to generate β cells for the cure of diabetes.
2021-07-01 | PXD018221 | JPOST Repository
Project description:Loss of functional beta-cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor Nkx6.1 in rat pancreatic islets induces beta-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates beta-cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated beta-cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in beta-cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c, resulting in degradation of the cell cycle inhibitor p21CIP1. These studies identify a new bipartite pathway for activation of beta-cell proliferation, suggesting several new targets for expansion of functional beta-cell mass. We set up a microarray using primary rat islets that were left untreated or transduced with adenoviruses overexpressing betagal or Nkx6.1 for 48 h.
2014-02-18 | E-GEOD-55077 | biostudies-arrayexpress
Project description:We identified a number of deregulated genes through transcriptome analysis on esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues. Our pathway enrichment analysis suggested that deregulated genes were strongly enriched in multiple functionally linked pathways known to be important in tumor cell proliferation (e.g., the p53 pathway and the cell-cycle pathway) and migration (e.g., the Notch pathway, the Wnt/β-catenin pathway).
2016-07-24 | GSE77531 | GEO
Project description:Objective : To study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled related protein (Frzb) compared to wild-type mice by transcriptome analysis. Methods : Gene-expression analysis of the articular cartilage and subchondral bone of 3 wild-type and 3 Frzb-/- mice was performed by microarray. Pathway analysis of differentially expressed genes between 3 wild-type and 2 Frzb-/- samples was explored with PANTHER, DAVID and GSEA bioinformatics tools. Activation of the WNT pathway was analyzed using western blot. The effects of Frzb gain and loss of function on chondrogenesis and cell proliferation was examined using ATDC5 micromasses and mouse ribcage chondrocytes. Results : Extracellular matrix-associated integrin and cadherin pathways, as well as WNT pathway genes were upregulated in Frzb-/- samples. Several WNT receptors, target genes, and other antagonists were upregulated, but no difference in active β-catenin was found. Analysis of ATDC5 cell micromasses overexpressing FRZB indicated an upregulation of aggrecan and Col2a1, and downregulation of molecules related to damage and repair in cartilage, Col3a1 and Col5a1. Silencing of Frzb resulted in downregulation of aggrecan and Col2a1. Pathways associated with cell cycle were downregulated. Ribcage chondrocytes derived from Frzb-/- mice showed decreased proliferation compared to wild-type cells. Conclusions : Our analysis provides evidence for tight regulation of WNT signaling, shifts in extracellular matrix components and effects on cell proliferation and differentiation in the articular cartilage - subchondral bone unit in Frzb-/- mice. These data further support an important role for FRZB in joint homeostasis and highlight the complex biology of WNT signaling in the joint. Gene-expression analysis of the articular cartilage and subchondral bone of 3 wild-type and 3 Frzb-/- mice was performed by microarray. Pathway analysis of differentially expressed genes between 3 wild-type and 2 Frzb-/- samples was explored with PANTHER, DAVID and GSEA bioinformatics tools.
2012-01-12 | E-GEOD-33656 | biostudies-arrayexpress
Project description:New insulin-producing pancreatic beta-cells are formed primarily by self-replication during adult life. To identify small molecules that can induce beta cell replication, a large chemical library was screened for proliferation of growth-arrested, reversibly immortalized mouse beta-cells using an automated high-throughput screening platform. A number of structurally diverse, active compounds were identified including phorbol esters, which likely act through protein kinase C, and a group of thiophene-pyrimidines that stimulate beta-cell proliferation by activating the Wnt signaling pathway. A group of dihydropyridine (DHP) derivatives was also shown to reversibly induce beta-cell replication in vitro by activating L-type calcium channels (LTCCs). Our data indicate that the LTCC agonist 2a affects the expression of genes involved in cell cycle progression and cellular proliferation. Furthermore, treatment of beta-cells with both LTCC agonist 2a and the Glp-1 receptor agonist Ex-4 showed an additive effect on beta-cell replication. The identification of small molecules that induce beta-cell proliferation suggests that it may be possible to reversibly expand other quiescent cells to overcome deficits associated with degenerative and/or autoimmune diseases. Experiment Overall Design: compound treatment and time course
2009-01-27 | E-GEOD-12802 | biostudies-arrayexpress
Project description:The analysis showed differences of transcriptomes between primary CDCs and immortalized CDCs as well as revealed TGF-β inhibitor-SB431542 treatment induced expression changes. We identified hTERT immortalization could result the cell proliferation and cell cycle related genes upregulation in iCDC. KEGG results demonstrated that TGF-β inhibitor SB431542 treatment could inhibit cardiomyopathy-related pathway which indicate TGF-β signaling pathway may serve as new target for cardiomyopathy therapy, and iCDC could be used as a heart-related chemicals screening.
2019-12-31 | GSE131765 | GEO
Project description:Loss of functional β-cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor Nkx6.1 in rat pancreatic islets induces β-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates β-cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated β-cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in β-cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c, resulting in degradation of the cell cycle inhibitor p21CIP1. These studies identify a new bipartite pathway for activation of β-cell proliferation, suggesting several new targets for expansion of functional β-cell mass.
2014-02-18 | GSE55077 | GEO