title: Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules.
abstract: Endodermal stem/progenitor cells have diverse potential applications in research and regenerative medicine, so a readily available source could have widespread uses. Here we describe derivation of human induced endodermal progenitor cells (hiEndoPCs) from gastrointestinal epithelial cells using a cocktail of defined small molecules along with support from tissue-specific mesenchymal feeders. The hiEndoPCs show clonal expansion in culture and give rise to hepatocytes, pancreatic endocrine cells, and intestinal epithelial cells when treated with defined soluble molecules directing differentiation. The hiEndoPC-derived hepatocytes are able to rescue liver failure in Fah-/-Rag2-/-mice after transplantation, and, unlike hESCs, transplanted hiEndoPCs do not give rise to teratomas. Since human gastric epithelial cells are readily available from donors of many ages, this conversion strategy can generate clonally expandable cell populations with a variety of potential applications, including personalized drug screening and therapeutic strategies for liver failure and diabetes.
authors.affiliation: Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China. Electronic address: wangyf1972@gmail.com.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell and Regenerative Medicine, South China Institute of Biomedicine, Guangzhou 510005, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Qin
authors.affiliation: Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell and Regenerative Medicine, South China Institute of Biomedicine, Guangzhou 510005, China.
authors.forename: Shuyong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jialei
authors.initials: J
authors.lastname: Duan
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of National Education, Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Huhhot 010000, China; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.affiliation: Tissue Engineering Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Chang
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing 100850, China; South China Research Center for Stem Cell and Regenerative Medicine, South China Institute of Biomedicine, Guangzhou 510005, China. Electronic address: peixt@nic.bmi.ac.cn.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Pei
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004386:Duodenum / Q000166:cytology; D044127:Epigenesis, Genetic / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013270:Stomach / Q000166:cytology*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D054852:Small Molecule Libraries