Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA330917 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Type 1 diabetes is characterized by the destruction of pancreatic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, overexpression of the master regulatory transcription factor Pax4 or loss of its counterplayer Arx are sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx and induce beta-cell characteristics in alpha cells. We show that the protein gephyrin is the mammalian target of these antimalaria drugs. Finally, we demonstrate that gephyrin-mediated enhancement of GABAA receptor signaling is the mechanism of action of these molecules in pancreatic transdifferentiation. Our results indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells.
2017-01-19 | GSE84714 | GEO
Project description:Type 1 diabetes is characterized by the destruction of pancrea tic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalaria drugs, and that enhancement of GABAA receptor signaling contributes to the mechanism of action of these molecules in pancreatic transdifferentiation. Our results in zebrafish, rodents and primary human pancreatic islets indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells.
2016-12-15 | GSE84592 | GEO
Project description:Artemisinins target GABAA receptor signaling and impair alpha cell identity
| PRJNA330538 | ENA
Project description:<p>The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC.</p>
2021-10-15 | MTBLS1925 | MetaboLights
Project description:Conversion of α-cells into insulin-producers upon β-cell loss is modulated by constitutive signals ensuring α-cell identity maintenance. Here, we characterized the plasticity of mouse α-cells by profiling their transcriptome at different time-points after massive β-cell ablation. Our results show that α-cells undergo stage-specific transcriptional changes 5- and 15-days post-diphtheria toxin (DT)-mediated β-cell ablation. At 5 days, α-cells transiently upregulate various genes associated with interferon signaling and proliferation, including Interferon Induced Protein with Tetratricopeptide Repeats 3 (Ifit3). Subsequently, at 15 days post β-cell ablation, α-cells undergo a transient downregulation of genes from several pathways including Insulin receptor, mTOR and MET signaling. These results pinpoint novel markers discriminating α-cells at different stages after acute β-cell loss, and highlight additional signaling pathways that could be involved in reprogramming the functional identity of α-cells.
2021-04-27 | GSE155519 | GEO
Project description:GPR30-mediated estrogen signaling in Estrogen Receptor alpha and beta negative SKBR3 breast cancer cells
| PRJNA106185 | ENA
Project description:Active estrogen receptor-alpha signaling in ovarian cancer
| PRJNA322076 | ENA
Project description:GLP-1 receptor signaling increases PCSK1 and beta-cell features in human alpha-cells
| PRJNA687419 | ENA
Project description:Transcriptional effects of glucocorticoid receptor alpha and beta signaling in zebrafish
| PRJNA267561 | ENA
Project description:β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling
| PRJNA188581 | ENA