Similar Datasets
Project description:Cpt1a WT vs Pdx1-cre Islet RNA
| PRJNA1091693 | ENA
Project description:Remarkable advancements in protocol development have been achieved to manufacture insulin-secreting islets from human pluripotent stem cells. Distinct from current approaches, we devised a tunable strategy to generate islet spheroids enriched for major islet cell types by incorporating PDX1+ cell budding morphogenesis into the differentiation process of staged transcriptional programming. In this process that appears to mimic normal islet morphogenesis, the differentiating islet spheroids self-organize with endocrine cells that are intermingled or arranged in a core-mantle architecture, accompanied with functional heterogeneity. Through in vitro modelling of human pancreas development, we illustrate the importance of PDX1 in eliciting cell budding morphogenesis, and the requirement for EphB3/4 signaling. We show how RFX6 deficiency affects pancreatic patterning and uncover an expected role of RFX6 in early pancreas morphology. The tunable differentiation system and stem cell-derived islet models described in this work may facilitate addressing fundamental questions in islet biology and probing human pancreas diseases.
2024-05-15 | GSE249020 | GEO
Project description:RNA-seq of Pdx1+ mouse Islet during development
| PRJEB8834 | ENA
Project description:Expression of CD40 in non-hematopoietic cells has been linked to inflammation. We presented evidence that CD40, a T-cell costimulatory molecule, is expressed in human β-cells and the engagement of CD40 in insulinoma cells activated the NFKB and ERK1/2 pathways. CD40 activation in human islets cells induced secretion of IL-8, MCP-1 and MIP-1 β, which is abrogated by inhibitors of NFkB and ERK1/2 inhibitors. In this study, we have studied gene expression mediated by CD40-CD40L interaction in islet cells. This approach identified 90 genes and transcripts exhibiting at least a 1.7 fold increase in their expression intensity after treatment with soluble CD40L. A significant number of genes were related to inflammation and oxidative stress. We have a strong overexpression of CXCL1 (Groα), CXCL2 (Mif2) and CXCL3; chemokines belonging to CXC family structurally related to Il-8. 11 genes were selected from this group and further quantified by Real Time PCR, including CXCL1. Activation of islet cells with CD40L induced the secretion of CXCL1 in a NFKB dependent manner. Engagement of CD40 in islet cells did not induce apoptosis, neither β-cell death and did not enhanced TNF-α mediated cell death as observed in insulinoma cells. CD40 activation in insulinoma cells, results in ERK1/2 dependent phsophorylation of synapsin I, a protein associated with the exocytosis machinery in neurons and β-cells. However, treatment of islets with soluble CD40L did not affect glucose induced insulin secretion. It has been reported that ductal cells always present in human islet preparations express CD40 constitutively (ref). We found that CD40-CD40L interaction in ductal cells, unlike in β-cells, induces secretion of diabetogenic cytokines IFNγ and TNF-α. Furthermore, incubation of islets containing ductal cells with CD40L decreased β-cells viability as assessed by measurement of their mitochondrial membrane potential Experiment Overall Design: We isolated islet cells from three patients. Part of islet cells from each patient has been treated with CD40L. We compared gene expression in treated cells vs untreated for each patient using dye-swap.
2008-10-20 | E-GEOD-8873 | biostudies-arrayexpress
Project description:pancreas islet single-cell RNA-seq
2018-10-23 | GSE117616 | GEO
Project description:We report the application of RNA-Seq to assess transcriptional profiles of S. aureus CC30 strains with allelic replacements (knockouts) of two genes in the LFR genomic islet: 1) fatty acid desaturase (fad) and 2) a MocR regulator. The overall results of our study suggest that the LFR islet enhances metabolic plasticity of the CC30 lineage which contributes to increased colonization, survival and persistence in the host.
2016-07-05 | GSE83995 | GEO
Project description:This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of alpha-cells (5%), beta-cells (92%), delta-cells (1%) and PP-cells (2%). We identified cell-type specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability (23%), low sequencing quality (13%) or contamination resulting in the detection of more than one islet hormone (64%). Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system. Single-cell RNA sequencing of mouse C57BL/6 pancreatic islet cells
2016-02-19 | E-GEOD-77980 | biostudies-arrayexpress
Project description:We report the application of RNA-Seq to assess transcriptional profiles of S. aureus CC30 strains with allelic replacements (knockouts) of two genes in the LFR genomic islet: 1) fatty acid desaturase (fad) and 2) a MocR regulator. The overall results of our study suggest that the LFR islet enhances metabolic plasticity of the CC30 lineage which contributes to increased colonization, survival and persistence in the host. The background strain used for these experiments was UAMS-1. Allelic replacements of fad and MocR were made in UAMS-1. The RNA-Seq experiments compared the transcriptional profiles of UAMS-1 vs. delta fad, and UAMS-1 vs. delta MocR. Two biological replicates were used for each RNA-Seq analysis.
2016-07-05 | E-GEOD-83995 | biostudies-arrayexpress
Project description:Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β cell function are controlled by the ATP-dependent Swi/Snf chromatin-remodeling coregulatory complex that physically associates with Pdx1, a diabetes-linked transcription factor essential to pancreatic morphogenesis and adult islet-cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, were required to compromise adult islet β cell activity, which included whole animal glucose intolerance, hyperglycemia and impaired insulin secretion. Notably, lineage-tracing analysis revealed that these Swi/Snf deficient β cells lost the ability to produce insulin and other key metabolic genes, yet the expression levels of many essential islet-enriched transcription factors were unaffected. Swi/Snf was necessary for Pdx1 binding to the insulin enhancer, demonstrating the importance of this association in mediating chromatin accessibility. These results illustrate how fundamental the Pdx1:Swi/Snf coregulator complex is in the pancreas and we discuss how disrupting their association could influence Type 1 and Type 2 diabetes susceptibility.
2019-06-01 | GSE128945 | GEO
Project description:Endocrine and exocrine pancreas tissues are both derived from the posterior foregut endoderm, however, the interdependence of these two cell types during their formation is not well understood. In this study, we generated mutant mice, in which the exocrine tissue is hypoplastic, in order to reveal a possible requirement for exocrine pancreas tissue in endocrine development and/or function. Since previous studies showed an indispensable role for Pdx1 in pancreas organogenesis, we used Elastase-Cre-mediated recombination to inactivate Pdx1 in the pancreatic exocrine lineage during embryonic stages. Along with exocrine defects, including impaired acinar cell maturation, the mutant mice exhibited substantial endocrine defects, including disturbed tip/trunk patterning of the developing ductal structure, a reduced number of Ngn3-expressing endocrine precursors, and ultimately fewer ? cells. Notably, postnatal expansion of the endocrine cell content was extremely poor, and the mutant mice exhibited impaired glucose homeostasis. These findings suggest the existence of an unknown but essential factor(s) in the adjacent exocrine tissue that regulates proper formation of endocrine precursors and the expansion and function of endocrine tissues during embryonic and postnatal stages.
| S-EPMC4758062 | biostudies-literature