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SRP154717
Homo sapiens
33 Downloadable Samples
Illumina HiSeq 2500
Description
Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. Here we report the development of a 3D blood vessel organoid culture system from human pluripotent stem cells. These human blood vessel organoids contain endothelial cells and pericytes that self-assemble into interconnected capillary networks enveloped by a basement membrane. Human blood vessel organoids transplanted into mice form a stable, perfused human vascular tree, including human arteries, arterioles and venules. Exposure of blood vessel organoids to hyperglycemia and inflammatory cytokines in vitro induced thickening of the basal membrane, a hallmark of human diabetic microangiopathy. Human blood vessel, exposed in vivo to a diabetic milieu in mice, also mimick the microvascular changes in diabetic patients. We finally performed a drug screen and uncovered ?-secretase and DLL4-Notch3 as key drivers of “diabetic” vasculopathy in human blood vessels in vitro and in vivo. Thus, organoids derived from human stem cells faithfully recapitulate the structure and function of human blood vessels and are amenable to model and identify drug targets for diabetic vasculopathy, which affects hundreds of millions of patients. Overall design: Vascular organoids were differentiated from iPSC cells and cultured in control, diabetic or diabetic media supplemented with the gamma-secretase inhibitor DAPT. Endothelial cells (CD31 positive) and pericytes (PDGFRbeta positive) were isolated by FACS and subjected to RNA Seq. Accordingly, CD31 positive endothelial cells and PDGFRbeta positive pericytes differentiated from iPS cells in 2D as a well as primary endothelial (HUVECS) and pericytes (Placenta) were FACS sorted and subjected to RNA Seq.
Publication Title
Human blood vessel organoids as a model of diabetic vasculopathy.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 4000
Description
Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. We report the development of 3D blood vessel organoids from human embryonic and induced pluripotent stem cells. These human blood vessel organoids contain endothelium, perivascular pericytes, and basal membranes, and self-assemble into lumenized interconnected capillary networks. We treat these vascular organoids with hyperglycemia and inflammatory cytokines in vitro, which leads to basement membrane thickening, a structural hallmark of diabetic patient. To compare differential gene expression we performed RNAseq on endothelial cells, derived from control (NG) or diabetic (DI) vascular organoids. Overall design: Vascular organoids were differentiated from human iPS cells and treated for 3 weeks with a diabetic media containing 75mM Glucose, 1ng/mL TNF-a, 1ng/mL IL6 (DI) or left untreated in 17mM Glucose (NG). Endothelial cells were FACS sorted for CD31 directly into Trizol and stored at -80°C before RNA preparation. The 2 NG and 2 DI are pools of sorted endothelial cells from multiple vascular organoids (>100) from 2 independent differentiations/treatments.
Publication Title
Human blood vessel organoids as a model of diabetic vasculopathy.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples