title: Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages.
abstract: Pancreatic β cells are of great interest for the treatment of type 1 diabetes. A number of strategies already exist for the generation of β cells, but a general approach for reprogramming nonendodermal cells into β cells could provide an attractive alternative in a variety of contexts. Here, we describe a stepwise method in which pluripotency reprogramming factors were transiently expressed in fibroblasts in conjunction with a unique combination of soluble molecules to generate definitive endoderm-like cells that did not pass through a pluripotent state. These endoderm-like cells were then directed toward pancreatic lineages using further combinations of small molecules in vitro. The resulting pancreatic progenitor-like cells could mature into cells of all three pancreatic lineages in vivo, including functional, insulin-secreting β-like cells that help to ameliorate hyperglycemia. Our findings may therefore provide a useful approach for generating large numbers of functional β cells for disease modeling and, ultimately, cell-based therapy.
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Ke
authors: K
authors: Li
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Saiyong
authors: S
authors: Zhu
authors: Diabetes Center, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Holger A
authors: HA
authors: Russ
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Shaohua
authors: S
authors: Xu
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Tao
authors: T
authors: Xu
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Yu
authors: Y
authors: Zhang
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: Tianhua
authors: T
authors: Ma
authors: Diabetes Center, School of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Matthias
authors: M
authors: Hebrok
authors: Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: sheng.ding@gladstone.ucsf.edu.
authors: Sheng
authors: S
authors: Ding
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects*; D065150:Cellular Reprogramming / Q000187:drug effects*; D004622:Embryo, Mammalian / Q000166:cytology; D004707:Endoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010179:Pancreas / Q000166:cytology*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries