title: Pancreatic Differentiation from Murine Embryonic Stem Cells.
abstract: Pluripotent stem cells are considered as a cell source for replacement therapies for pancreatic beta cells and other organs.We identified tetrabenazine (TBZ), vesicular monoamine transporter 2 (VMAT2) inhibitor as a promoter of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Ngn3-positive endocrine progenitor cells. A cell-permeable cAMP analog, dBu-cAMP promotes beta cell maturation in late stage of differentiation. The induced beta cells can secrete insulin in a glucose-dependent manner.Our protocol consists of a three -step differentiation process. ES cell recapitulate embryonic developmental processes in vitro. Therefore, the ES cell differentiation system is a useful model for the understanding of molecular mechanism of beta-cell differentiation and are useful for application for future regenerative medicine.
authors.affiliation: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, 860-0811, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakano
authors.affiliation: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, 860-0811, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shiraki
authors.affiliation: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, 860-0811, Japan. skume@kbio.titech.ac.jp.|Program for Leading Graduate Schools "HIGO (Health life science; Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, 860-0811, Japan. skume@kbio.titech.ac.jp.|Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa, 226-8503, Japan. skume@kbio.titech.ac.jp.
authors.forename: Shoen
authors.initials: S
authors.lastname: Kume
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D018398:Homeodomain Proteins / Q000032:analysis; D051379:Mice; D010179:Pancreas / Q000166:cytology*; D013747:Tetrabenazine / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors
chemical_list: D018398:Homeodomain Proteins; C493453:Slc18a2 protein, mouse; D015534:Trans-Activators; D050493:Vesicular Monoamine Transport Proteins; C084010:pancreatic and duodenal homeobox 1 protein; D013747:Tetrabenazine
keywords: GSIS; Pancreatic differentiation; VMAT2 inhibitor