Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells

Using 10x Genomics Chromium Single Cell 3’ RNAseq platform, we sequenced human stem cell derived pancreatic islet cells during different stages of development and maturation process. We optimized a protocol for pancreatic endocrine differentiation, particularly focusing on the final, extended maturation stage during which significant reorganization of the cytoarchitecture of islet-like aggregates took place correlating with a remarkable maturation of glucose-induced insulin secretion. The transcriptomic changes during the time-course were combined with detailed physiological studies including dynamic insulin secretion assays, respirometry measurements, electrophysiological profiling as well as imaging of calcium and cAMP signaling and exocytosis. 18 scRNAseq samples were analyzed.