Patchseq Data of T1D Donor Islets vs ND Matched Controls
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE270484 | GEO | 2024/06/25
REPOSITORIES: GEO
Similar Datasets
Project description:Patchseq Data of T1D Donor Islets vs ND Matched Controls
| PRJNA1126733 | ENA
Project description:Will be added/updated once the manuscript is finalized.
2013-10-26 | GSE24953 | GEO
Project description:Type 2 diabetes is associated with defective insulin secretion and reduced β-cell mass. Available treatments provide a temporary reprieve, but secondary failure rates are high, making insulin supplementation necessary. Reversibility of b-cell failure is a key translational question. Here, we reverse-engineered and interrogated pancreatic islet-specific regulatory networks to discover T2D-specific subpopulations characterized by metabolic-inflexibility and endocrine-progenitor/stem cell features. Single-cell gain- and loss-of-function and glucose-induced Ca++ flux analyses of top candidate MR in islet cells validated transcription factor BACH2 and associated epigenetic effectors as a key driver of T2D cell states. BACH2 knockout in T2D islets reversed cellular features of the disease, restoring a non-diabetic phenotype. BACH2-immunoreactive islet cells increased ~4-fold in diabetic patients, confirming the algorithmic prediction of clinically relevant subpopulations. Treatment with a BACH inhibitor lowered glycemia and increased plasma insulin levels in diabetic mice, and restored insulin secretion in diabetic mice and human islets. The findings suggest that T2D-specific populations of failing b-cells can be reversed and indicate pathways for pharmacological intervention, including via BACH2 inhibition.
2021-11-11 | GSE136887 | GEO
Project description:We recently described the persistence of detectable serum proinsulin in a large majority of individuals with longstanding type 1 diabetes (T1D), including individuals with undetectable serum C-peptide. Here, we sought to further explore the mechanistic etiologies of persistent proinsulin secretion in T1D at the level of the islet, using tissues obtained from human donors. Immunostaining for proinsulin and insulin was performed on human pancreatic sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) collection (n = 24). Differential proinsulin processing enzyme expression was analyzed using mass spectrometry analysis of human islets isolated from pancreatic sections with laser capture microdissection (n = 6). Proinsulin processing enzyme mRNA levels were assessed using quantitative real-time PCR in isolated human islets (n = 10) treated with or without inflammatory cytokines. Compared to nondiabetic controls, immunostaining among a subset (4/9) of insulin positive T1D donor islets revealed increased numbers of cells with proinsulin-enriched, insulin-poor staining. T1D donor islets also exhibited increased proinsulin fluorescence intensity relative to insulin fluorescence intensity. Laser capture microdissection followed by mass spectrometry revealed reductions in the proinsulin processing enzymes prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE) in T1D donors. Twenty-four hour treatment of human islets with inflammatory cytokines reduced mRNA expression of the processing enzymes PC1/3, PC2, and CPE. Taken together, these data provide new mechanistic insight into altered proinsulin processing in long-duration T1D and suggest that reduced β cell prohormone processing is associated with proinflammatory cytokine-induced reductions in proinsulin processing enzyme expression.
| S-EPMC6783367 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Manuscript title: Fraxinus excelsior updated long-read genome reveals the importance of MADS-box genes in tolerance mechanisms against ash dieback, G3:Genes|Genomes|Genetics
2025-03-03 | GSE214554 | GEO
Project description:Type 1 Diabetes (T1D) is characterized by autoimmune-mediated destruction of insulin-producing beta-cells. Recent research has focused on the role of the innate immune system in initiating this process. To investigate this further, we used m6A-profiling of human islets from non-diabetic individuals and the human beta-cell line EndoC-bH1 treated with PBS or interleukin 1 beta and interferon alpha, as well as established T1D patients. Our findings reveal that N6-Methyladenosine (m6A) is a mechanism that helps protect beta-cells by accelerating the decay of mRNA from the 2'-5'-oligoadenylate synthetase (OAS) genes, which controls the antiviral innate immune response at the onset of T1D. These results provide insight into the adaptive safeguarding mechanisms of beta-cells and the role of m6A in T1D development, highlighting potential targets for therapeutic interventions.
2024-01-01 | GSE228267 | GEO
Project description:A new genome of Fraxinus excelsior was assembled using a hybrid approach combining Nanopore and Illumina data (BioProject PRJNA865134, SAMN30100368, genome JANJPF000000000 ). Methylation was also assessed in the genome. Manuscript title: Fraxinus excelsior updated long-read genome reveals the importance of MADS-box genes in tolerance mechanisms against ash dieback, G3:Genes|Genomes|Genetics
2025-03-03 | GSE214553 | GEO
Project description:Using a large collection of diverse viral immunomodulatory proteins, and comprehensive human protein microarray libraries, we identify more than 51 virus-host interactions that suggest new immunoregulatory strategies. Full description of this study will be detailed in Martinez-Martin et al., Nat Communications, under review (this information will be updated when manuscript is accepted).
2016-03-04 | GSE78518 | GEO
Project description:Diabetes results from insufficient insulin secretion as a result of dysfunction to β-cells within the islet of Langerhans. Elevated glucose causes β-cell membrane depolarization and action potential generation, voltage gated Ca2+ channel activation and oscillations in free-Ca2+ activity ([Ca2+]), triggering insulin release. Nuclear Factor of Activated T-cell (NFAT) is a transcription factor that is regulated by increases in [Ca2+] and calceineurin (CaN) activation. NFAT regulation links cell activity with gene transcription in many systems, and within the β-cell regulates proliferation and insulin granule biogenesis. However the link between the regulation of β-cell electrical activity and oscillatory [Ca2+], with NFAT activation and downstream transcription is poorly understood. In this study we test whether dynamic changes to β-cell electrical activity and [Ca2+] regulates NFAT activation and downstream transcription. In cell lines, mouse islets and human islets, including those with type2 diabetes, we applied both agonists/antagonists of ion channels together with optogenetics to modulate β-cell electrical activity. Both glucose-induced membrane depolarization and optogenetic-stimulation triggered NFAT activation, and increased transcription of NFAT targets and intermediate early genes (IEGs). Importantly only conditions in which slow sustained [Ca2+] oscillations were generated led to NFAT activation and downstream transcription. In contrast in human islets from donors with type2 diabetes NFAT activation by glucose was diminished, but rescued upon pharmacological stimulation of electrical activity. Thus, we gain insight into the specific patterns of electrical activity that regulate NFAT activation and gene transcription and how this is disrupted in diabetes.
2020-06-23 | GSE152970 | GEO