Efficient Generation of NKX6-1+ Pancreatic Progenitors from Multiple Human Pluripotent Stem Cell Lines

• DOI: 10.1016/j.stemcr.2015.02.017
• Publication Date: 2015-04-05T20:37:30Z
• Authors: M. Cristina Nostro; Farida Sarangi; Chaoxing Yang; Andrew Holland; Andrew G. Elefanty; Edouard G. Stanley; Dale L. Greiner; Gordon Keller
• Keywords: Niacinamide; Pluripotent Stem Cells; 0301 basic medicine; Medicine (General); QH301-705.5; Organogenesis; 610; Models, Biological; Article; Cell Line; Immunophenotyping; Islets of Langerhans; Mice; 03 medical and health sciences; R5-920; Animals; Humans; Biology (General); Pancreas; Homeodomain Proteins; Epidermal Growth Factor; Cell Differentiation; Activins; Gene Expression Regulation; Carrier Proteins; Signal Transduction

Human pluripotent stem cells (hPSCs) represent a renewable source of pancreatic beta for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate development in hPSC differentiation cultures. In study, we demonstrate combination epidermal growth factor (EGF) nicotinamide induces generation NKX6-1+ progenitors from all lines tested. Furthermore, show size population is regulated by duration treatment with retinoic acid, fibroblast 10 (FGF10), inhibitors bone morphogenetic protein (BMP) hedgehog pathways. When transplanted into NOD scid gamma (NSG) recipients, these differentiate give rise exocrine endocrine cells, including monohormonal insulin+ cells. Together, findings provide an efficient reproducible strategy generating highly enriched populations hPSC-derived cell studies aimed at further characterizing their developmental potential vivo deciphering maturation vitro.