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Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293267 | GEO | 2025/05/08

REPOSITORIES: GEO

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Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells [scRNA-seq]

Project description:Dysfunction of pancreatic alpha cells contributes to the pathophysiology of diabetes. Features of diabetic alpha cell dysfunction include glucagon hypersecretion, defects in proglucagon processing, and altered transcriptomic profile. The lack of an in vitro human alpha cell model has prevented the investigation, and potential correction, of these dysfunctional phenotypes. Here, we show that induction of endoplasmic reticulum stress in stem cell-derived alpha (SC-α) cells induces hypersecretion of glucagon. ER stress also increases the secretion of glicentin and expression of GLP-1, peptides produced by alternate cleavage of proglucagon by the prohormone convertase 1 (PC1/3) enzyme. Additionally, ER stress establishes a diabetic transcriptional state in SC-α cells characterized by downregulation of MAFB, as well as glycolysis and oxidative phosphorylation pathways. We show that sunitinib, a tyrosine kinase inhibitor, protects SC-α cells against the ER stress-induced glucagon hypersecretion phenotype. Thus, SC-α cell model can advance our knowledge of islets in health and diabetes.

2025-05-08 | GSE293265 | GEO

Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells

Project description:Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells

| PRJNA1243443 | ENA

Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells [Bulk RNA-seq]

2025-05-08 | GSE293266 | GEO

Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells [scRNA-seq]

Project description:Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells [scRNA-seq]

| PRJNA1243445 | ENA

Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells [Bulk RNA-seq]

Project description:Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells [Bulk RNA-seq]

| PRJNA1243446 | ENA

Conditional modeling of MLL-AF9 induced leukemia revealed a stem cell derived aggressive disease

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-27 | E-GEOD-65384 | biostudies-arrayexpress

Disease modeling of pulmonary fibrosis using human iPS cell-derived alveolar organoids

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-19 | GSE172123 | GEO

Modeling Preeclampsia using human induced pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-15 | GSE159480 | GEO

Modeling human retinoblastoma using embryonic stem cell-derived retinal organoids.

Project description:Retinoblastoma (Rb) is the most prevalent intraocular malignancy in early childhood. Traditional models are unable to accurately recapitulate the origin and development of human Rb. Here, we present a protocol to establish a novel human Rb organoid (hRBO) model derived from genetically engineered human embryonic stem cells (hESCs). This hRBO model exhibits properties highly consistent with human primary Rb and can be used effectively for dissecting the origination and pathogenesis of Rb as well as for screening of potential therapies. For complete details on the use and execution of this protocol, please refer to Liu et al. (2020).

| S-EPMC8058612 | biostudies-literature

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease.

Project description:BackgroundEndothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction.MethodsWe generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups.ResultsIn both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs.ConclusionESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD.

| S-EPMC8685359 | biostudies-literature

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