Generation of stomach tissue from mouse embryonic stem cells

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 demon...

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Veröffentlicht in:Nature cell biology 2015-08, Vol.17 (8), p.984-993
Hauptverfasser: Noguchi, Taka-aki K., Ninomiya, Naoto, Sekine, Mari, Komazaki, Shinji, Wang, Pi-Chao, Asashima, Makoto, Kurisaki, Akira
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container_issue 8
container_start_page 984
container_title Nature cell biology
container_volume 17
creator Noguchi, Taka-aki K.
Ninomiya, Naoto
Sekine, Mari
Komazaki, Shinji
Wang, Pi-Chao
Asashima, Makoto
Kurisaki, Akira
description 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. Noguchi and colleagues report the generation of stomach-like tissue from mouse embryonic stem cells. They show that the tissue contains all stomach-specific cell types and secretes acid and digestive enzyme.
doi_str_mv 10.1038/ncb3200
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subjects 13/100
13/106
14/1
14/28
14/63
38/61
631/136/2060
631/136/532/1360
631/136/532/2117
631/136/756/1462
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Animals
Cancer Research
Cell Biology
Cell culture
Cell differentiation
Cell Differentiation - drug effects
Cell Lineage
Cell research
Developmental Biology
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Embryonic Stem Cells - physiology
Gastric Acid - metabolism
Gastric Mucosa - metabolism
Gastritis, Hypertrophic - genetics
Gastritis, Hypertrophic - metabolism
Gastritis, Hypertrophic - pathology
Gastrointestinal diseases
Gene Expression Profiling
Gene Expression Regulation, Developmental
Hedgehog Proteins - metabolism
Histamine - pharmacology
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Innovations
Life Sciences
Mice
Mice, Inbred ICR
Organogenesis
Pepsinogen A - metabolism
Phenotype
Regenerative Medicine - methods
Spheroids, Cellular
Stem Cells
Stomach - cytology
Stomach - drug effects
Stomach - physiology
Time Factors
Tissue Engineering - methods
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
Transforming Growth Factor alpha - genetics
Transforming Growth Factor alpha - metabolism
title Generation of stomach tissue from mouse embryonic stem cells
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