RRC ID 69934
著者 Uehara K, Koyanagi-Aoi M, Koide T, Itoh T, Aoi T.
タイトル Epithelial-derived factors induce muscularis mucosa of human induced pluripotent stem cell-derived gastric organoids.
ジャーナル Stem Cell Reports
Abstract Human gastric development has not been well studied. The generation of human pluripotent stem cell-derived gastric organoids (hGOs) comprising gastric marker-expressing epithelium without an apparent smooth muscle (SM) structure has been reported. We modified previously reported protocols to generate hGOs with muscularis mucosa (MM) from hiPSCs. Time course analyses revealed that epithelium development occurred prior to MM formation. Sonic hedgehog (SHH) and TGF-β1 were secreted by the epithelium. HH and TGF-β signal inhibition prevented subepithelial MM formation. A mechanical property of the substrate promoted SM differentiation around hGOs in the presence of TGF-β. TGF-β signaling was shown to influence the HH signaling and mechanical properties. In addition, clinical specimen findings suggested the involvement of TGF-β signaling in MM formation in recovering gastric ulcers. HH and TGF-β signaling from the epithelium to the stroma and the mechanical properties of the subepithelial environment may influence the emergence of MM in human stomach tissue.
巻・号 17(4)
ページ 820-834
公開日 2022-4-12
DOI 10.1016/j.stemcr.2022.02.002
PII S2213-6711(22)00091-1
PMID 35245440
PMC PMC9023774
MeSH Hedgehog Proteins Humans Induced Pluripotent Stem Cells* Mucous Membrane Organoids* Stomach Transforming Growth Factor beta
IF 6.032
リソース情報
ヒト・動物細胞 201B7(HPS0063)