title: Human pancreatic beta-like cells converted from fibroblasts.
abstract: Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.
authors.forename: Saiyong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Holger A
authors.initials: HA
authors.lastname: Russ
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Ma
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.
authors.forename: Shibing
authors.identifier: http://orcid.org/0000-0001-8592-3477
authors.initials: S
authors.lastname: Tang
authors.affiliation: Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hebrok
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.|Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D007328:Insulin; D005947:Glucose