Transciptomics and Epigenomics of Immune evasive human islet-like organoids

We generated human islet-like organoids (HILOs) from induced pluripotent stem cells and show that activation of the non-canonical WNT pathway drives a metabolic maturation step necessary for robust glucose-stimulated insulin secretion. These functionally mature HILOs containing multiple endocrine cell types maintain glucose homeostasis upon transplantation into diabetic NOD-SCID mice. Furthermore, we show that overexpression of PD-L1 generates immune evasive HILOs able to maintain glucose homeostasis in immune-competent type 1 diabetic mice for 50 days.