Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

Beta cells are the sole source of insulin in our body, yet we do not understand how they mature into fully functional, glucose-responsive beta cells. We discovered a persistent population of immature beta cells that is marked by the absence of Ucn3 and is functionally immature. We generated transcriptomes of these immature beta cells, along with mature beta cells and the mixed pool of non-beta cells from the same islets. This enables a systematic comparison across thousands of genes between two distinct maturation stages of the beta cell. FACS purified immature or mature beta cells, or double negatives from the same islets. Islets were isolated from bitransgenic offspring of a cross between Ins1-H2b-mCherry (Jax # 028589) and Ucn3-eGFP. Immature beta cells are mCherry single positive, mature beta cells are eGFP and mCherry co-positive. Non beta cells are negative for mCherry and eGFP. Islets from replicate groups of 10 to 12 bitransgenic females for each group were pooled to obtain sufficient material. Pooled islets were dissociated, sorted and collect in Trizol for RNA isolation and library construction.