E-MEXP-1140
Ontology highlight
ABSTRACT:
TISSUE(S): Islet Of Langerhans, Pancreas
PROVIDER: E-MEXP-1140 | ExpressionAtlas | 2025-01-22
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MEXP-1140-analysis-methods.tsv | Tabular | |||
| E-MEXP-1140-atlasExperimentSummary.Rdata | Rdata | |||
| E-MEXP-1140-configuration.xml | Xml | |||
| E-MEXP-1140-percentile-ranks.tsv | Tabular | |||
| E-MEXP-1140.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 84 |
Similar Datasets
Project description:Genes involved in distinct diabetes types suggest shared disease mechanisms. We show that rare ONECUT1 coding variants cause monogenic recessive diabetes (neonatal or very early-onset, syndromic) in two unrelated patients, and monogenic dominant diabetes (early adult-onset) in heterozygous relatives of these and 13 additional unrelated cases. Patients heterozygous for rare ONECUT1 coding variants define a subgroup of T2D with early-onset diabetes and other features. In addition, common regulatory ONECUT1 variants are associated with multifactorial T2D. Directed differentiation of human pluripotent stem cells to the pancreatic lineage revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. We uncovered that ONECUT1 activates the pro-endocrine genes NKX6.1 and NKX2.2 through binding to their cis-regulatory elements. Globally, ONECUT1-directed gene transcription occurs in association with major islet transcription factors, at clusters of pancreas- and endocrine-specific enhancers within open chromatin. ONECUT1 regulates a transcriptional and epigenetic machinery critical for proper endocrine pancreatic development, involved in a spectrum of diabetes, monogenic recessive and dominant, and multifactorial.
2021-11-03 | PXD018887 | Pride
Project description:Type 1 diabetes is an autoimmune disease caused by the destruction of the insulin producing beta cells. We characterized the gene expression profile of pancreatic tissue from four type 1 diabetes patients (Cases 1-4), who died at different stages of the disease (onset and longstanding) by microarray analysis. All samples from patients and controls were obtained after death, at the time of organ donation. Pancreatic blocks from the four diabetic patients and three organ donors (Controls 1-3) were obtained and snap frozen. At the same time, islets from Cases 1 and 4 were isolated from a piece of the pancreas tail by enzymatic digestion (using automated method and handpicking) and snap frozen. Islets from three different organ donors (Controls 4-6) were obtained similarly to those of the diabetic patients. Both pancreatic blocks and islets were stored in liquid nitrogen until the mRNA extraction. For pancreas gene expression profiles, we compared data from three blocks of each of the four type 1 diabetic pancreas with pancreases data from the Controls 1-3. For islets expression profile, we compared data from Cases 1 and 4 islets with islets data from the Controls 4-6. <br><br>
2009-12-01 | E-MEXP-1140 | biostudies-arrayexpress
Project description:MODY8 (maturity-onset diabetes of the young, type 8) is a dominantly inherited monogenic form of diabetes associated with frameshift mutations in the carboxyl ester lipase (CEL) gene expressed by pancreatic acinar cells. Patients carrying the mutation develop childhood-onset exocrine pancreas dysfunction followed by the manifestation of diabetes during adulthood. However, it is unclear how CEL mutations cause diabetes. Here we report the transfer of proteins from acinar cells to β-cells as a form of crosstalk between exocrine and endocrine cells. Human β-cells showed a relatively higher propensity for internalizing the mutant versus the wild-type CEL protein. Following internalization, the mutant protein formed stable intracellular aggregates leading to β-cell secretory dysfunction. To investigate the effects in vivo, we transplanted stem cell-derived wild-type or mutant pancreatic progenitors into independent mice and generated insulin-secreting β-like cells and CEL-expressing acinar-like cells. While the β-like cells derived from wild-type stem cells responded to glucose, the β-like cells derived from mutant stem cells were dysfunctional secondary to the accumulation of intracellular mutant CEL protein. Analysis of pancreas sections from a MODY8 patient also revealed the presence of CEL protein in the few extant β-cells. This study provides compelling evidence for the mechanism by which a mutant gene expressed specifically in acinar cells promotes dysfunction and loss of β-cells to cause diabetes.
2021-12-03 | GSE185430 | GEO
Project description:Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes (T1D), yet the functional consequences to the host of this dysbiosis is unknown. Here, we have performed a metaproteomic analysis of 103 stool samples from subjects that either had recent-onset T1D, were high-risk autoantibody positive or low-risk autoantibody negative relatives of individuals with beta cell autoimmunity or healthy individuals to identify signatures in host and microbial proteins associated with disease risk. Multivariate modelling analysis demonstrated that both human host proteins and microbial derived proteins could be used to differentiate new-onset and seropositive individuals from low-risk and healthy controls. Significant alterations were identified between subjects with T1D or islet autoimmunity versus autoantibody negative and control subjects in the prevalence of individual host proteins associated with exocrine pancreas function, inflammation and mucosal function. Data integrationIntegrative analysis combining the metaproteomic data with bacterial abundance showed that taxa that were depleted in new-onset T1D patients were positively associated with host proteins involved in maintaining function of the mucous barrier, microvilli adhesion and exocrine pancreas. These data support the notion that T1D patients have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset T1D patients and show for the first time that this dysfunction is present in high-risk individuals prior to disease onset. Our data has identified a unique T1D-associated signature in stool that may be useful as a means to monitor disease progression or response to therapies aimed at restoring a healthy microbiota.
2018-11-07 | PXD008870 | Pride
Project description:OBJECTIVE: Novel biomarkers of disease progression after type 1 diabetes onset are needed. RESEARCH DESIGN AND METHODS: We profiled peripheral blood (PB) monocyte gene expression in 6 healthy subjects and 16 children with type 1 diabetes diagnosed ~3 months previously, and analyzed clinical features from diagnosis to 1 year. RESULTS: Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy controls, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA1c levels during the first year, compared to patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g. induction of HIF1A, DDIT3, DDIT4 and GRP78). qPCR quantitation of a 9-gene panel correlated with glycaemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. CONCLUSIONS: A PB gene expression signature correlates with glycaemic control in the first year after diabetes diagnosis, and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset, and systemic stresses as contributors to innate immune function in type 1 diabetes. CD14+ monocytes from a total of 16 children with recent-onset type 1 diabetes and 6 adult healthy controls were profiled in 2 independent microarrays.
2012-05-31 | E-GEOD-33440 | biostudies-arrayexpress
Project description:Transcription profiling of myotubes from patients with type 2 diabetes
| PRJNA112829 | ENA
Project description:Introduction: Maturity-onset Diabetes of the Young (MODY) is a rare form of diabetes and arises from mutations in key regulatory genes of the pancreatic beta-cell, leading to their functional impairment and early-onset diabetes. Research into PDX1-MODY, a form of MODY caused by mutations in the PDX1 gene, enhances understanding of gene-specific mechanisms underlying glucose dysregulation and provides insights into possible approaches to restore normal metabolic function. However, no currently published mouse model accurately depicts the genetic cause of PDX1-MODY in human patients. Methods: Using CRISPR-Cas9 technology, we generated the first mouse model carrying one of the most prevalent pathological PDX1 point mutation found in human patients, P33T, and conducted an 18-week in vivo phenotyping experiment assessing homozygous PDX1P33T and wild type littermates on both chow and high fat diet (HFD). Additionally, transcriptomic and proteomic analyses were performed on isolated pancreatic islets. Islet architecture was investigated via fluorescent microscopy. Result: Contrary to expectations, our comprehensive phenotypic analysis of the mouse model carrying the homozygous PDX1P33T point mutation revealed no significant differences in metabolic parameters compared to wild-type controls, and no pathological outcomes were observed as seen in human patients. Notably, male PDX1P33T mice exhibited an increase in islet size and number on chow diet but failed to adapt respectively on HFD. Discussion: Our work indicates substantial differences between mouse and human PDX1 function in the pancreas. Further refinement of animal models is necessary to better elucidate the pathophysiology of PDX1-MODY. Ultimately, this study emphasizes the complexities involved in translating human pathologies to animal models, serving as a reminder that findings generated in mice may not always be easily translated to humans.
2025-10-14 | PXD066252 | Pride
Project description:Metaproteomic investigation to unveil human gut microbiota features possibly linked to the onset of type 1 diabetes
2022-06-21 | MSV000089691 | MassIVE
Project description:OBJECTIVE: Novel biomarkers of disease progression after type 1 diabetes onset are needed. RESEARCH DESIGN AND METHODS: We profiled peripheral blood (PB) monocyte gene expression in 6 healthy subjects and 16 children with type 1 diabetes diagnosed ~3 months previously, and analyzed clinical features from diagnosis to 1 year. RESULTS: Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy controls, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA1c levels during the first year, compared to patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g. induction of HIF1A, DDIT3, DDIT4 and GRP78). qPCR quantitation of a 9-gene panel correlated with glycaemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. CONCLUSIONS: A PB gene expression signature correlates with glycaemic control in the first year after diabetes diagnosis, and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset, and systemic stresses as contributors to innate immune function in type 1 diabetes.
2012-06-01 | GSE33440 | GEO
Project description:Emerging evidence points towards an intricate relationship between the pandemic coronavirus disease 2019 (COVID-19) and diabetes. While diabetes is associated with an increased risk of severe COVID-19, new-onset type 1 diabetes (T1D) has been observed in COVID-19 patients, convoluting diabetes as both a risk factor and consequence of COVID-19. Understanding the mechanistic relationship between COVID-19 and T1D is an urgent and critical public health challenge. One pressing question is whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2, as T1D is a direct consequence of β-cell depletion. Here, we find that the SARS-CoV-2 receptor, ACE2 and its related entry factors, TMPRSS2, NRP1, and TRFC, are expressed in β-cells, with the latter two selectively present within β-cells. We discover that SARS-CoV-2 has selective cellular tropism for human pancreatic β-cells both ex vivo and in patients with COVID-19. We demonstrate that SARS-CoV-2 infection lowers the abundance of insulin within the pancreas, attenuates glucose-stimulated insulin secretion, and induces β-cell apoptosis. Finally, phosphoproteomic and pathway analysis suggests a SARS-CoV-2 stimulated signature for induction of apoptosis-associated signaling pathways in β-cells, similar to that seen in T1D. Taken together, our study demonstrates that SARS- CoV-2 can directly cause pancreatic islet impairment by killing β-cells, providing a mechanistic explanation for why T1D develops in COVID-19 patients.
2021-07-24 | PXD025629 | Pride