Single-Cell Transcriptome Profiling Reveals ß Cell Maturation in Stem Cell-Derived Islets after Transplantation

SC-ß cells and native ß cells from cadaveric islets have different transcriptome profiles. In this study, we demonstrate that SC-ß cells can acquire mature gene signatures via transplantation in mice for 6 months. MAFA, a marker for mature ß cells, is expressed and resulted in significant improvements in insulin release and glucose regulation in diabetic mice. Overall design: Stem cell derived islets were generated and transplanted into the kidney capsule of each diabetic mouse. We harvested the kidneys with SC islets from mice at 6 months post-transplantation and excised graft sections for tissue dissociation. We used the mouse cell depletion kit to enrich human cells from the extracted graph cell suspension. Isolated and enriched human cell samples were then submitted for single cell RNA sequencing. We performed this with 5 mice, including SC islet cells generated from the Hues8 and IPS lines and pre-transplated in Vitro Stage 6 control.