Similar Datasets
Project description:Infection of SC-beta cells with coxsackievirus B4 (CVB)
| PRJNA605945 | ENA
Project description:The goal of this study was to identify transcriptional changes in SC-beta and SC-endothelial cells pre and post IFN-gamma stimulation. Specifically, to characterize the differential expression of immune cell ligands in these cells with respect to a partial inflammatory stimulus.
2022-12-23 | GSE200021 | GEO
Project description:Stem cell-derived β (SC-β) cells are an emerging regenerative therapy to compensate for loss of functional β cell mass in diabetes. Glucose-stimulated insulin secretion in SC-β cells is variable in vitro but stabilizes after transplantation and maturation under the kidney capsule of mice. We identified mechanisms correlated with functional maturation using RNA-sequencing and co-expression network analysis. In vivo maturation enhanced glucose-stimulated but not basal insulin secretion, up-regulated β cell hormones IAPP and ADCYAP1, increased expression of maturation markers MAFA, UCN3, and SIX2, and resolved endocrine identity of incompletely specified polyhormonal cells produced during differentiation. Transplantation promoted calcium signalling, induced exocytotic machinery supporting hormone secretion and improved stimulus-secretion coupling that fine-tunes insulin secretion. Growth hormone signalling emerged as candidate driver of in vivo maturation and was confirmed in vitro. Also, a large co-expression module correlated with HbA1c and was enriched in genes up-regulated during in vivo maturation but down-regulated in hyperglycaemic and palmitate stress conditions, suggesting that transcriptional maturation of SC-β cells in vivo mirrors processes lost in diabetic β cells.
2019-08-19 | GSE135944 | GEO
Project description:SC-beta Cell in vivo Maturation
| PRJNA560712 | ENA
Project description:Islet transplantation for treatment of diabetes is limited by availability of donor islets and requirements for immunosuppression. Stem cell-derived islets might circumvent these issues. SC-islets effectively control glucose metabolism post transplantation, but do not yet achieve full function in vitro with currently published differentiation protocols. We aimed to identify markers of mature subpopulations of SC-β cells by studying transcriptional changes associated with in vivo maturation of SC-β cells using RNA-seq and co-expression network analysis. The β cell-specific hormone islet amyloid polypeptide (IAPP) emerged as the top candidate to be such a marker. IAPP+ cells had more mature β cell gene expression and higher cellular insulin content than IAPP- cells in vitro. IAPP+ INS+ cells were more stable in long-term culture than IAPP- INS+ cells and retained insulin expression after transplantation into mice. Finally, we conducted a small molecule screen to identify compounds that enhance IAPP expression. Aconitine up-regulated IAPP and could help to optimize differentiation protocols.
2024-04-15 | GSE263366 | GEO
Project description:RNA Seq of IAPP expressing SC-β cells
| PRJNA1096942 | ENA
Project description:Numerous serotypes which belong to the genus Enterovirus (EV) show variability in their virulence and clinical manifestations. They are also known to undergo changes caused by mutations and recombination during their circulation in the environment and the population. Various EV serotypes are prevalent in groundwater, wastewater and surface waters. Our previous studies showed that oral infection induces pancreatitis depending on specific conditions, such as gravidity, in an outbred murine model. Our aim in the present study was to further explore the pancreatic histopathology in an outbred mouse model following oral infection with clinical isolates from a patient who had aseptic meningitis and an isolate from a treated-sewage sample recovered from the residential area of the patient. The isolates were identified as coxsackievirus B4 (CVB4) in tissue culture. The CVB4 sewage-isolate induced pancreatitis after oral infection. In contrast, pancreatitis was absent following infection with the clinical isolates. Comparison of polyprotein sequences showed that the treated-sewage strains differed from the patient's isolates by 9 and 11 amino acids. We conclude that the isolates of clinical and environmental origin differed in their pathogenic properties and showed genetic variation.
| S-EPMC8346287 | biostudies-literature
Project description:Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the GAD β-cell antigen. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by anti-CVB T cells. Thus, our in-vitro and ex-vivo data suggest limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CVB-reactive CD8+ T cells provide biomarkers to follow response to infection and vaccination.
2023-08-19 | PXD042711 | Pride
Project description:We collected total RNA from both Ishikawa-02 SC and Ishikawa-02 shSOX2 and examined mRNA expression profile, comprehensively.
2018-05-18 | GSE114582 | GEO