Homo sapiens
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-22097
PROVIDER: PRJNA128915 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcription profiling by array of human pancreatic beta cells transplanted into mice
2025-01-24 | E-GEOD-22097 | ExpressionAtlas
Project description:Islet transplantation exposes beta cells to mild hyperglycemia and to the abnormal environment of the transplant site. These conditions may affect beta cells and induce the expression of genes involved in beta cell damage. Gene expression profile of human beta cells exposed to mild hyperglycemia by transplantation into ICR-SCID mice was evaluated and compared with the gene profile of beta cells obtained from non-diabetic subjects. We found that the transplanted beta cells showed an unfolded protein response (UPR). There was upregulation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress. Among them, increased expression of genes coding XBP-1; the chaperone proteins PDIA4, Bip, and Grp94; and the ER degradation proteins EDEM1 and EDEM2. ERdj4 and DNA-JC3 were also upregulated. JUK had downregulated expression. The PERK and ATF-6 arms of the ER stress response had many downregulated genes in transplanted islets. The PERK's substrates, EIF2A and NRF2, showed markedly reduced expression, as downregulated was the expression of CReP. Other downregulated genes included HERP2, IRS-2, CHOP and C/EBP-beta. In the transplanted beta cells there was significantly decreased expression of ATF-6, as well as the downstream gene products CHOP and HERP2. There was increased expression of HRD1, which exerts an antiapoptotic effect by degrading unfolded proteins. In conclusion human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins. Frozen sections were obtained from pancreases of non-diabetic subjects at surgery and from human islets transplanted into ICR-SCID mice for 4 weeks. β cell enriched samples were obtained by laser capture microdissection. RNA was extracted, amplified and subjected to microarray analysis.
2010-06-08 | E-GEOD-22097 | biostudies-arrayexpress
Project description:Islet transplantation exposes beta cells to mild hyperglycemia and to the abnormal environment of the transplant site. These conditions may affect beta cells and induce the expression of genes involved in beta cell damage. Gene expression profile of human beta cells exposed to mild hyperglycemia by transplantation into ICR-SCID mice was evaluated and compared with the gene profile of beta cells obtained from non-diabetic subjects. We found that the transplanted beta cells showed an unfolded protein response (UPR). There was upregulation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress. Among them, increased expression of genes coding XBP-1; the chaperone proteins PDIA4, Bip, and Grp94; and the ER degradation proteins EDEM1 and EDEM2. ERdj4 and DNA-JC3 were also upregulated. JUK had downregulated expression. The PERK and ATF-6 arms of the ER stress response had many downregulated genes in transplanted islets. The PERK's substrates, EIF2A and NRF2, showed markedly reduced expression, as downregulated was the expression of CReP. Other downregulated genes included HERP2, IRS-2, CHOP and C/EBP-beta. In the transplanted beta cells there was significantly decreased expression of ATF-6, as well as the downstream gene products CHOP and HERP2. There was increased expression of HRD1, which exerts an antiapoptotic effect by degrading unfolded proteins. In conclusion human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins.
2010-06-02 | GSE22097 | GEO
Project description:Microarray comparing gene expression changes between control, normoglycaemic mice, and mice expressing the human neonatal diabetes mutation Kir6.2-V59M in pancreatic beta-cells left diabetic for 2 weeks
2016-10-13 | E-MTAB-5086 | ExpressionAtlas
Project description:Gene expression profile of pancreatic -cells from COUP-TFII-deficient mice
2015-09-18 | E-GEOD-30526 | ExpressionAtlas
Project description:Type 1 and type 2 diabetes (T1D and T2D) share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, while beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alter the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role for beta cell fragility in genetic predisposition to diabetes.
2016-02-24 | PXD000859 | Pride
Project description:Transcription profiling by high throughput sequencing of pancreatic beta cells from wild type and Abcc8 knockout mice
2019-05-14 | E-MTAB-4726 | ExpressionAtlas
Project description:Generating insulin-producing β-cells from human induced pluripotent stem cells is a promising cell replacement therapy aimed at improving or curing certain forms of diabetes. Nevertheless, despite important recent advances, the efficient production of functionally mature β-cells is yet to be achieved, with most current differentiation protocols generating a heterogeneous population comprising of subpopulation of cells expressing different islet hormones, including hybrid polyhormonal entities. A solution to this issue is transplanting end-stages differentiating cells into living hosts, which was demonstrated to majorly improve β-cell maturation. Yet, to date, the cellular and molecular mechanisms underlying the transplanted cells response to the in vivo environment exposure was not yet properly characterized. Here we use global proteomics and large-scale imaging techniques aimed at demultiplexing and filtering cellular processes and molecular signatures modulated by the immediate in vivo effect. We show that in vivo exposure swiftly confines in vitro generated human pancreatic progenitors to single hormone expression. The global proteome landscape of the transplanted cells was closer to the one presented by native human islets, especially in regard to energy metabolism and redox balance. Moreover our study indicates a possible link between these processed and certain epigenetic regulators involved in maintenance and propagation of the islet cells identity. Pathway analysis predicted HNF1A and HNF4A as key regulators controlling the in vivo islet-promoting response, with experimental evidence confirming their involvement in confining islet cell identity. To our knowledge this is the first study demultiplexing the immediate response of the transplanted pancreatic progenitors to in vivo exposure.
2020-02-12 | PXD015955 | Pride
Project description:Objective: The loss of insulin-secreting β-cells, ultimately characterizing most diabetes forms, demands the development of cell replacement therapies. The common endpoint for all ex vivo strategies is transplantation into diabetic patients. However, the effects of hyperglycemia environment on the transplanted cells were not yet properly assessed. Thus, the main goal of this study was to characterize global effect of brief and prolonged in vivo hyperglycemia exposure on the cell fate acquisition and maintenance of transplanted human pancreatic progenitors. Methods: To rigorously study the effect of hyperglycemia, in vitro differentiated human induced pluripotent stem cells (hiPSC)-derived pancreatic progenitors were xenotransplanted in normoglycemic and diabetic NSG RIP-DTR mice. The transplants were retrieved after one-week or one-month exposure to overt hyperglycemia and analyzed by large-scale microscopy or global proteomics. For this study we pioneer the use of the NSG RIP-DTR system in the transplantation of hiPSC, making use of its highly reproducible specific and absolute β-cell ablation property in the absence of inflammation or other organ toxicity. Results: Here we show for the first time that besides the presence of an induced oxidative stress signature, the cell fate and proteome landscape response to hyperglycemia was different, involving largely different mechanisms, according to the period spent in the hyperglycemic environment. Surprisingly, brief hyperglycemia exposure increased the bihormonal cell number by impeding the activity of specific islet lineage determinants. Moreover it activated antioxidant and inflammation protection mechanisms signatures in the transplanted cells. In contrast, the prolonged exposure was characterized by decreased numbers of hormone+ cells, low/absent detoxification signature, augmented production of oxygen reactive species and increased apoptosis. Conclusion: Hyperglycemia exposure induced distinct, period-dependent, negative effects on xenotransplanted human pancreatic progenitor, affecting their energy homeostasis, cell fate acquisition and survival.
2020-02-12 | PXD015071 | Pride
Project description:RNA-seq of human islet pancreatic cells to identify eQTL loci
2020-04-24 | E-ENAD-42 | ExpressionAtlas