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Nat Cell Biol. 2015 Aug;17(8):984-93. doi: 10.1038/ncb3200. Epub 2015 Jul 20.

Generation of stomach tissue from mouse embryonic stem cells.

Author information

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.
3
Department of Anatomy, Saitama Medical University, Saitama 350-0495, Japan.
4
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.
5
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.

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.

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PMID:
26192439
DOI:
10.1038/ncb3200
[Indexed for MEDLINE]
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