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

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

PROVIDER: PRJNA890151 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21890244_1.fastq.gz	Fastqsanger.gz
	SRR21890244_2.fastq.gz	Fastqsanger.gz
	SRR21890245_1.fastq.gz	Fastqsanger.gz
	SRR21890245_2.fastq.gz	Fastqsanger.gz
	SRR21890246_1.fastq.gz	Fastqsanger.gz

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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

Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids

Project description:Blood vessels play a critical role in pancreatic islet function, yet current methods for deriving islet organoids from human pluripotent stem cells (SC-islets) lack vasculature. We engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts 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. Furthermore, vascularization accelerated diabetes reversal post-engraftment of a subtherapeutic SC-islet dose. We show that vasculature leads to formation of an islet-like basement membrane that contributes to functional improvement of SC-β-cells. Furthermore, scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β cells, and correspondingly, BMP4 enhanced the SC-β cell Ca2+ response and insulin secretion. Vascularized SC-islets will enable further studies of crosstalk between β-cells and ECs and will serve as an in vitro platform for disease modeling and therapeutic testing.

2025-08-20 | GSE276815 | GEO

Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids

Project description:Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids

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Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling

Project description:Cell replacement therapies hold great therapeutic potential. Nevertheless, our knowledge of the mechanisms governing the developmental processes is limited, impeding the quality of differentiation protocols. Generating insulin-expressing cells in vitro is no exception, with the guided series of differentiation events producing heterogeneous cell populations that display mixed pancreatic islet phenotypes and immaturity. The achievement of terminal differentiation ultimately requires the in vivo transplantation of, usually, encapsulated cells. Here we show the impact of cell confinement on the pancreatic islet signature during the guided differentiation of alginate encapsulated human induced pluripotent stem cells (hiPSCs). Our results show that encapsulation improves differentiation by significantly reshaping the proteome landscape of the cells towards an islet-like signature. Pathway analysis is suggestive of integrins transducing the encapsulation effect into intracellular signalling cascades promoting differentiation. These analyses provide a molecular framework for understanding the confinement effects on hiPSCs differentiation while confirming its importance for this process.

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Global phosphoproteomic analysis revealed the regulation of Drak2 in islet function

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Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

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Mouse islet ATG7 beta-cell knockout LC-MS/MS

Project description:We knocked out the critical autophagy enzyme, ATG7, in the β-cells of mice (ATG7Δβ-cell) then monitored blood glucose to assess the phenotype induced by this KO model. We found that all ATG7Δβ-cell mice developed diabetes between 11-15 weeks of age. We isolated islets from ATG7Δβ-cell and littermate control mice several weeks prior to diabetes development (7-10 weeks of age) and performed bulk islet proteomics. The purpose of this experiment was to understand the islet biological process pathways altered by dysfunctional β-cell autophagy in the ATG7Δβ-cell model.

2025-01-22 | PXD060032 | Pride

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