Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7995510_1.fastq.gz | Fastqsanger.gz | |||
| SRR7995510_2.fastq.gz | Fastqsanger.gz | |||
| SRR7995520_1.fastq.gz | Fastqsanger.gz | |||
| SRR7995520_2.fastq.gz | Fastqsanger.gz | |||
| SRR7995511_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 38 |
Similar Datasets
Project description:Islet transplantation is an ideal option for diabetes while early graft lose serves as a major obstacle. Human umbilical cord mesenchymal stem cells (hucMSC) have multiple functions including the maintenance of cellular homeostasis. However, it is unknown whether extracellular vesicles (EVs) derived from hucMSC (hucMSC-EVs) provide protective effects against transplant-related trauma-induced islet injury. Here, we isolated and purified hucMSC-EVs, and found that hucMSC-EVs promoted grafted islet survival, and enhanced glycemic control following co-transplantation in a syngeneic streptozotocin (STZ)-induced mouse model of diabetes. After co-cultured for 12 h or 24 h, labelled hucMSC-EVs with PKH67 were readily internalized by NIT-1 β cells and islets. In tunicamycin (Tm) and thapsigargin (Tg) induced specific endoplasmic reticulum stress (ERS) cell injury models, hucMSC-EVs treatment improved cell viability and β cells function both in NIT-1 cells and ex vivo primary islets. Bulk RNA-seq demonstrated that hucMSC-EVs treatment significantly involved in ERS and the negative regulated mitochondrial apoptotic pathway. While ERS promoted interactions between endoplasmic reticulum (ER) and mitochondria, hucMSC-EVs alleviated ERS, maintained calcium homeostasis, and improved mitochondrial energy metabolism. Notably, the downregulation of XBP1 by hucMSC-EVs fine-tuned ER-mitochondria communication via reducing inositol-1,4,5-trisphosphate receptors at mitochondria-associated membranes (MAMs). Reduced XBP1 also activated Nrf2, restoring mitochondrial calcium homeostasis under ERS. miRNA analysis identified miR-182-5p enriched in hucMSC-EVs that specifically targeted XBP1 mRNA, leading to its degradation and downregulation. These findings demonstrate that hucMSC-EVs protect grafted islets by blocking XBP1 and restoring calcium homeostasis, thus suggesting their potential as a cell-free therapy for improving islet transplantation outcomes.
2025-11-02 | GSE296373 | GEO
Project description:Identifying cis-regulatory elements is important to understand how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation marks (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ~18,000 putative promoters (several hundred novel and islet-active). Surprisingly, active promoter marks were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (non-promoter) regulatory elements, 47% are islet-unique and 22% are CTCF-bound. These findings present a global snapshot of the human islet epigenome and should provide functional context for non-coding variants emerging from genetic studies of T2D and other pancreatic islet disorders. Three different islet samples were tested for DNase I hypersensitivity by DNase-Seq. Five different primary pancreatic islet samples were evaluated for several chromatin modifications (H3K4me3, H3K4me1, H3K79me2) by ChIP-seq. One islet sample was evaluated for CTCF binding via ChIP-seq, All ChIP-seq samples have both non-specific IP (GFP) and input DNA controls.
2010-11-02 | E-GEOD-23784 | biostudies-arrayexpress
Project description:We anticipated that the identification of cis-regulatory regions active in pancreatic islets would help increase our understanding of islet biology and the pathology of diabetes. Towards this end we used histone H3 lysine 4 monomethylation-based nucleosome predictions genome-wide, in conjunction with binding data for PDX1, FOXA2, MAFA, and NEUROD1, to identify 3,654 putative enhancers that are H3K4me1-enriched uniquely in islets as compared to 14 other tissue or cell-types. We show that these islet-specific enhancers are associated with genes with significantly higher islet specificity than genes associated with non-specific enhancers. Further, islet-specific enhancers were not enriched for typical active or repressive histone methylations in embryonic stem cells and liver, suggesting they are formed by de novo histone methylation during pancreas development. We also identify a subset of enhancers bivalently marked by both H3K4me1 and H3K27me3 in adult pancreatic islets. Further, we show that islet-specific enhancers triple- or quadruple- bound by PDX1, MAFA, NEUROD1 and/or FOXA2 are associated with genes with particularly high islet-specificity, and that these loci are enriched in regions with functional activity in islet cell types. Finally, we demonstrate that cytokines reduce H3K4me1 enrichment levels at selected triple- or quadruple-bound islet-specific enhancers, suggesting that epigenetic changes may contribute to cytokine-induced b-cell dysfunction. In conjunction with data from Hoffman et al Genome Research 2010, an analysis of histone modifications and transcription factor binding sites to identify enhancer regions
2011-06-30 | E-GEOD-30298 | biostudies-arrayexpress
Project description:Mitochondrial energy metabolism and function are key processes underlying the pathophysiology of insulin resistance and predisposition to type 2 diabetes. This is because mitochondria produce most of the energy required by the cell. Impaired energy production, use of energy stores and mitochondrial dysfunction are major features in metabolic diseases. Nevertheless, it remains uncertain how mitochondrial dysfunction can cause, contribute to, or result in insulin resistance and metabolic diseases. Furthermore there is growing evidence from genetic and genome wide-association studies that genetic variation in mtDNA contributes to these common metabolic diseases (Wallace, 2005), however there has been essentially no in vivo functional validation for these findings. Therefore we generated a mouse model homozygous for a polymorphism in the Mrpp3 gene identified in the French Canadian population responsible for 22% of mitochondrial epitranscriptome variation, with likely consequences on metabolism. We investigated the in vivo effects of the polymorphism on mitochondrial function and metabolism in mice fed normal and high fat diet. We identify that the polymorphism reduces the efficiency of mitochondrial RNA processing and this is most pronounced in the pancreas that results in insulin resistance. The MRPP3 protein containing the Asn434Ser polymorphism associates specifically with the calcium antiporter LETM1 preventing effective release of calcium from mitochondria and consequently impairs insulin release from the pancreatic islet cells of these mice. Reduction in insulin secretion and enlarged pancreatic islet size results in lower circulating levels of insulin that causes insulin resistance and liver steatosis. Our findings reveal for the first time the link between mitochondrial gene regulation and insulin resistance via calcium signaling.
2021-09-24 | GSE161978 | GEO
Project description:loss of Men1 in mouse pancreatic islet cells alters the epigenetic landscape of a subset of target genes. H3K4me3 ChIP-seq from either mouse pancreatic islets or mouse pancreatic islet tumors harvested at different stages.
2015-04-16 | E-GEOD-63020 | biostudies-arrayexpress
Project description:This pilot phase I trial studies the side effects and best dose of CPI-613 when given together with fluorouracil in treating patients with colorectal cancer that has spread to other parts of the body and cannot be removed by surgery. CPI-613 may kill tumor cells by turning off their mitochondria. Mitochondria are used by tumor cells to produce energy and are the building blocks needed to make more tumor cells. By shutting off these mitochondria, CPI-613 deprives the tumor cells of energy and other supplies that they need to survive and grow in the body. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPI-613 with fluorouracil may kill more tumor cells.
| 2173777 | ecrin-mdr-crc
Project description:The intrahepatic milieu is inhospitable to intraportal islet allografts, limiting their applicability to ameliorate Type 1 Diabetes (T1D). Islet viability in the subcutaneous space represents an unfulfilled paradigm that is crucial to ensure widespread adoption and safety of clinical islet transplantation. Herein we report that human islets transplanted subcutaneously uniformly promote long-term euglycemia when admixed with a device-free Islet Viability Matrix (IVM), through a previously unknown anti-apoptotic mechanism.
2020-06-01 | GSE145593 | GEO
Project description:Identifying cis-regulatory elements is important to understand how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation marks (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ~18,000 putative promoters (several hundred novel and islet-active). Surprisingly, active promoter marks were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (non-promoter) regulatory elements, 47% are islet-unique and 22% are CTCF-bound. These findings present a global snapshot of the human islet epigenome and should provide functional context for non-coding variants emerging from genetic studies of T2D and other pancreatic islet disorders.
2010-11-02 | GSE23784 | GEO
Project description:We anticipated that the identification of cis-regulatory regions active in pancreatic islets would help increase our understanding of islet biology and the pathology of diabetes. Towards this end we used histone H3 lysine 4 monomethylation-based nucleosome predictions genome-wide, in conjunction with binding data for PDX1, FOXA2, MAFA, and NEUROD1, to identify 3,654 putative enhancers that are H3K4me1-enriched uniquely in islets as compared to 14 other tissue or cell-types. We show that these islet-specific enhancers are associated with genes with significantly higher islet specificity than genes associated with non-specific enhancers. Further, islet-specific enhancers were not enriched for typical active or repressive histone methylations in embryonic stem cells and liver, suggesting they are formed by de novo histone methylation during pancreas development. We also identify a subset of enhancers bivalently marked by both H3K4me1 and H3K27me3 in adult pancreatic islets. Further, we show that islet-specific enhancers triple- or quadruple- bound by PDX1, MAFA, NEUROD1 and/or FOXA2 are associated with genes with particularly high islet-specificity, and that these loci are enriched in regions with functional activity in islet cell types. Finally, we demonstrate that cytokines reduce H3K4me1 enrichment levels at selected triple- or quadruple-bound islet-specific enhancers, suggesting that epigenetic changes may contribute to cytokine-induced b-cell dysfunction.
2011-06-30 | GSE30298 | GEO