Efficient generation of NKX6-1(+) pancreatic progenitors from multiple human pluripotent stem cell lines

M Cristina Nostro, Farida Sarangi, Chaoxing Yang, Andrew M Holland, Andrew G Elefanty, Edouard G Stanley, Dale L Greiner, Gordon Keller

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148 Citations (Scopus)

Abstract

Human pluripotent stem cells (hPSCs) represent a renewable source of pancreatic beta cells for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate pancreatic development in hPSC differentiation cultures. In this study, we demonstrate that the combination of epidermal growth factor (EGF) and nicotinamide signaling induces the generation of NKX6-1(+) progenitors from all hPSC lines tested. Furthermore, we show that the size of the NKX6-1(+) population is regulated by the duration of treatment with retinoic acid, fibroblast growth factor 10 (FGF10), and inhibitors of bone morphogenetic protein (BMP) and hedgehog signaling pathways. When transplanted into NOD scid gamma (NSG) recipients, these progenitors differentiate to give rise to exocrine and endocrine cells, including monohormonal insulin(+) cells. Together, these findings provide an efficient and reproducible strategy for generating highly enriched populations of hPSC-derived beta cell progenitors for studies aimed at further characterizing their developmental potential in vivo and deciphering the pathways that regulate their maturation in vitro.
Original languageEnglish
Pages (from-to)591 - 604
Number of pages14
JournalStem Cell Reports
Volume4
Issue number4
DOIs
Publication statusPublished - 2015

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