Mus musculus
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ABSTRACT:
PROVIDER: PRJNA252783 | ENA |
REPOSITORIES: ENA
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Project description:The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes
| PRJNA252758 | ENA
Project description:The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes (Min6 cells)
| PRJNA252782 | ENA
Project description:The inability of the beta-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, beta-cell replication is one of the mechanisms thought to cause the expansion of beta-cell mass. Efforts to treat diabetes require knowledge of the pathways that drive facultative beta-cell proliferation in vivo. A robust physiological stimulus of beta-cell expansion is pregnancy, and identifying the mechanisms underlying this stimulus may provide therapeutic leads for the treatment of type 2 diabetes. The peak in beta-cell proliferation during pregnancy occurs on day 14.5 of gestation in mice. Using advanced genomic approaches, we globally characterize the gene expression signature of pancreatic islets on day 14.5 of gestation during pregnancy. We identify a total of 1,907 genes as differentially expressed in the islet during pregnancy. We demonstrate that the islet's ability to compensate for relative insulin deficiency during metabolic stress is associated with the induction of both proliferative and survival pathways. A comparison of the genes induced in three different models of islet expansion suggests that diverse mechanisms can be recruited to expand islet mass. The identification of many novel genes involved in islet expansion during pregnancy provides an important resource for diabetes researchers to further investigate how these factors contribute to the maintenance of not only islet mass, but ultimately beta-cell mass.
2010-06-26 | E-MTAB-120 | biostudies-arrayexpress
Project description:Type 1 diabetes (T1D) is an immune-mediated disease that leads to β cell dysfunction and death. However, the contribution of β cells in this process remains unclear. To understand how islet-derived pro-inflammatory signaling pathways contribute to diabetes pathogenesis, we generated inducible islet-specific Alox15 knockout mice on the NOD background. We report that islet-specific deletion of Alox15 induced a substantial increase of β-cell mass and decreased islet insulitis, and ultimately lead to a protection against spontaneous autoimmune diabetes in NOD mice. Single cell RNA-sequencing and mass spectrometry analysis revealed that islet-specific knockout of Alox15 leads to an increase of β cells expressing Pd-l1 and promotes an anti-inflammatory phenotype in myeloid cells and T cells inside the islets. Furthermore, islet- specific Alox15 deletion enhances the expansion of M2-like macrophages and regulatory T cells in the pancreatic islets and pancreatic lymph nodes. Together, these results lead to the conclusion that proinflammatory signals produced by β cells allows these cells to express immunoregulators that protects these cells of immune cell attack and promote β cell survival.
2021-02-11 | GSE166572 | GEO
Project description:The remarkable differentiation capacity of pluripotent stem cells into any adult cell types have enabled researchers to model human embryonic development and disease process in dishes, as well as deriving specialized cells for replacing damaged tissues. Type 1 diabetes is a degenerative disease characterized by autoimmune destruction of the insulin-producing beta islet cells in the pancreas. Recent advances have led to the establishment of different methods to direct differentiation of human or mouse pluripotent stem cells toward beta cell lineages. However, existing strategies have not yet succeeded in generating fully functional beta cells in vitro. Thus, it remains a major challenge to identify novel regulators of beta cell differentiation and maturation, and the islet-specific genetic and epigenetic regulatory networks are logical targets. To obtain a comprehensive view of the microRNA expression pattern during in vitro directed differentiation of hPSC into pancreatic beta islet cells, we collected 16 samples of 6 stages of differentiated derivatives, 2 samples of human fetal pancreas and 5 samples of purified human beta islet cells for analysis. With these samples, we performed genome-wide microRNA expression profiling using the Illumina Human v2 MicroRNA Expression BeadChips (1,146 assays).
2012-11-07 | E-GEOD-42093 | biostudies-arrayexpress
Project description:Pancreatic islet beta cell heterogeneity has been identified, which plays a pivotal role in the pathological alterations of pancreatic islets in type 2 diabetes (T2D) mice. However, pathological alterations of beta cells in type 2 diabetes (T2D) mice remain to be investigated. We isolated pancreatic islets from the control and T2D mice and conducted scRNA-seq analysis using the 10x Genomics platform. Pathological alterations of beta cells in T2D were also explored.
2022-04-09 | GSE200531 | GEO
Project description:Pancreatic islet cells are critical for maintaining normal blood glucose levels and their malfunction underlies diabetes development and progression. We used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic α-, β-, δ- and PP cells from non-diabetic and type 2 diabetes organ donors. We identified cell type specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human α- and β-cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community.
2016-08-31 | GSE81608 | GEO
Project description:Pancreatic beta cell senescence occurs during the development of Type 1 Diabetes. To model the transcriptional responses of islet cells to DNA damage, we previously developed a human islet culture model in which the DNA damage response and senescence can be induced via double strand-breaks with the agent bleomycin. Here, we report the transcriptome-wide changes in human pancreatic islet cells following bleomycin exposure.
2021-06-08 | GSE176324 | GEO
Project description:Blood glucose levels are tightly controlled by the coordinated action of at least five cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 diabetes (T2D). Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet dysfunction, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single cell transcriptomes for 617 islet cells after profiling ~1000 cells from non-diabetic (ND) and T2D human organ donors. Analyses of non-diabetic single cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell type-specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. Grant ID: Award No. W81XWH-16-1-0130 Grant title: Peer Reviewed Medical Research Program Funding Source: Assistant Secretary of Defense for Health Affairs Affiliation: Jackson Laboratory for Genomic Medicine, Farmington, CT Name: Michael Stitzel
2016-11-09 | GSE86469 | GEO