title: miRNA-302 facilitates reprogramming of human adult hepatocytes into pancreatic islets-like cells in combination with a chemical defined media.
abstract: The direct conversion of one cell type to another without an intermediate pluripotent stage is required for regenerative therapies. The ventral pancreas and liver share a common developmental origin. Recent studies have shown that hepatocytes could be induced to transdifferentiate into insulin-producing cells. In this paper, we showed a new strategy to achieve the direct conversion of human hepatocytes into surrogate β cells. Hepatocytes were transfected with microRNA-302 (miR-302) mimic and Pdx1, Ngn3 and MafA expressed plasmids, followed by a chemical-defined culture system for maturation of insulin-secreting cells. Co-transfection of miR-302 mimic increased the transcription of pancreatic development-related genes (Sox17, Foxa2, and endogenous Pdx1). Furthermore, at the end of this treatment, hepatocytes became insulin expressed cells that released the hormone in response to a physiological glucose change in vitro. This work shows that miR-302 participation may facilitates the conversion of adult hepatocytes into pancreatic islets-like cells.
authors.affiliation: FuJian Provincial Key Laboratory of Transplant Biology, Fuzhou General Hospital/ or Dongfang Hospital, Xiamen University, Fuzhou 350025, China. Electronic address: junlu.heather@yahoo.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: FuJian Provincial Key Laboratory of Transplant Biology, Fuzhou General Hospital/ or Dongfang Hospital, Xiamen University, Fuzhou 350025, China.
authors.forename: Huiyue
authors.initials: H
authors.lastname: Dong
authors.affiliation: FuJian Provincial Key Laboratory of Transplant Biology, Fuzhou General Hospital/ or Dongfang Hospital, Xiamen University, Fuzhou 350025, China.
authors.forename: Lingjing
authors.initials: L
authors.lastname: Lin
authors.affiliation: FuJian Provincial Key Laboratory of Transplant Biology, Fuzhou General Hospital/ or Dongfang Hospital, Xiamen University, Fuzhou 350025, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
authors.affiliation: FuJian Provincial Key Laboratory of Transplant Biology, Fuzhou General Hospital/ or Dongfang Hospital, Xiamen University, Fuzhou 350025, China.
authors.forename: Lianghu
authors.initials: L
authors.lastname: Huang
authors.affiliation: FuJian Provincial Key Laboratory of Transplant Biology, Fuzhou General Hospital/ or Dongfang Hospital, Xiamen University, Fuzhou 350025, China. Electronic address: tanjm156@xmu.edu.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tan
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media; D017931:DNA Primers; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction
chemical_list: D003470:Culture Media; D017931:DNA Primers; C532169:MIRN302A microRNA, human; D035683:MicroRNAs
keywords: Hepatocytes; Insulin; Pancreatic islets-like cells; miR-302