title: Generation of stomach tissue from mouse embryonic stem cells.
abstract: Successful pluripotent stem cell differentiation methods have been developed for several endoderm-derived cells, including hepatocytes, β-cells and intestinal cells. However, stomach lineage commitment from pluripotent stem cells has remained a challenge, and only antrum specification has been demonstrated. We established a method for stomach differentiation from embryonic stem cells by inducing mesenchymal Barx1, an essential gene for in vivo stomach specification from gut endoderm. Barx1-inducing culture conditions generated stomach primordium-like spheroids, which differentiated into mature stomach tissue cells in both the corpus and antrum by three-dimensional culture. This embryonic stem cell-derived stomach tissue (e-ST) shared a similar gene expression profile with adult stomach, and secreted pepsinogen as well as gastric acid. Furthermore, TGFA overexpression in e-ST caused hypertrophic mucus and gastric anacidity, which mimicked Ménétrier disease in vitro. Thus, in vitro stomach tissue derived from pluripotent stem cells mimics in vivo development and can be used for stomach disease models.
authors.affiliation: Graduate School of Life and Environmental Sciences, The University of Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Taka-aki K
authors.initials: TK
authors.lastname: Noguchi
authors.affiliation: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8562, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ninomiya
authors.affiliation: Graduate School of Life and Environmental Sciences, The University of Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Sekine
authors.affiliation: Department of Anatomy, Saitama Medical University, Saitama 350-0495, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.affiliation: Graduate School of Life and Environmental Sciences, The University of Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Pi-Chao
authors.initials: PC
authors.lastname: Wang
authors.affiliation: 1] Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8562, Japan [2] Life Science Center of Tsukuba Advanced Research Alliance, The University of Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.affiliation: 1] Graduate School of Life and Environmental Sciences, The University of Tsukuba, Ibaraki 305-8577, Japan [2] Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8562, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurisaki
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005758:Gastritis, Hypertrophic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D038081:Organogenesis; D020116:Pepsinogen A / Q000378:metabolism; D010641:Phenotype; D044968:Regenerative Medicine / Q000379:methods*; D018874:Spheroids, Cellular; D013270:Stomach / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C095587:Barx1 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C587886:TGFA protein, human; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; D006632:Histamine; D020116:Pepsinogen A