RESEARCH ARTICLE Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for

Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation during pan-creatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets. NGN3 protein can be detected in the adult rodent pancreas only following certain types of injury, when it is transiently expressed by exocrine cells undergoing reprogramming to an endocrine cell fate. Here, NGN3 protein can be detected in 2 % of acinar and duct cells in living biopsies of histologically normal adult human pancreata and 10 % in cadaveric biopsies of organ donor pancreata. The per-centage and total number of NGN3+ cells increase during culture without evidence of prolif-eration or selective cell death. Isolation of highly purified and viable NGN3+ cell populations can be achieved based on coexpression of the cell surface glycoprotein CD133. Transcrip-tome and targeted expression analyses of isolated CD133+ / NGN3+ cells indicate that they are distinct from surrounding exocrine tissue with respect to expression phenotype and Notch signaling activity, but retain high level mRNA expression of genes indicative of acinar and duct cell function. NGN3+ cells have an mRNA expression profile that resembles tha