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Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection

ABSTRACT: Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection

PROVIDER: PRJNA1040752 | ENA |

REPOSITORIES: ENA

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Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [snATACseq.VMI]

Project description:Immune cells play critical roles in causing host damage in various diseases, including infectious diseases. However, there is a paucity of human models to study immune-mediated host damage. Here, we systematically analyzed the changes in immune cell composition for COVID-19 pancreatic autopsy samples using the GeoMx spatial RNA and protein platform and found accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets upon SARS-CoV-2 or Coxsackievirus B4 (CVB4) infection identified the activation of proinflammatory macrophages and pyroptosis in β cells. To distinguish whether the virus or proinflammatory macrophages mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids, containing pancreatic endocrine cells, endothelial cells, and macrophages. Both pancreatic β cells and endothelial cells in VMI organoids demonstrated improved marker expression and function compared to separately cultured cells. Additionally, proinflammatory macrophages in VMI organoids were found to induce β cell pyroptosis. Further mechanistic studies identified TNFSF12-TNFRSF12A as a contributor to proinflammatory macrophage-mediated β cell pyroptosis. Together, this study established a hPSC-derived VMI organoid as a valuable tool for studying immune cell-mediated host damage and uncovered previous unknown mechanism of β cell damage in viral infection.

2024-08-08 | GSE247808 | GEO

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [scRNAseq.VMI]

2024-08-08 | GSE247807 | GEO

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [scRNAseq.islets]

2024-08-08 | GSE247806 | GEO

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [bulkRNAseq]

2024-08-08 | GSE247805 | GEO

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [scRNAseq.islets]

Project description:Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [scRNAseq.islets]

| PRJNA1040757 | ENA

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [scRNAseq.VMI]

Project description:Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [scRNAseq.VMI]

| PRJNA1040756 | ENA

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [bulkRNAseq]

Project description:Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [bulkRNAseq]

| PRJNA1040758 | ENA

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [snATACseq.VMI]

Project description:Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection [snATACseq.VMI]

| PRJNA1040755 | ENA

Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic beta cell Pyroptosis upon Viral Infection

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

2024-08-08 | GSE247809 | GEO

Vascularization of pluripotent stem cell-derived islet organoids improves β-cell function

Project description:Blood vessels play a critical role in pancreatic islet health and function, yet current culture methods to generate islet organoids from human pluripotent stem cells (SC-islets) lack a vascular component. Here, we engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts both in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+ influx into SC-β-cells; a hallmark of β-cell function that is blunted in non-vascularized SC-islets. We show that an islet-like basement membrane is formed by vasculature and contributes to the functional improvement of SC-β-cells. Furthermore, cell-cell communication networks based on scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β-cells. Correspondingly, BMP4 augmented the SC-β-cell Ca2+ response and insulin secretion. The here-described vascularized SC-islet models will enable further studies of crosstalk between β-cells and ECs and serve as an in vivo-mimicking platform for disease modeling and therapeutic testing.

2023-05-01 | GSE215376 | GEO

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