title: Mini-gut organoids: reconstitution of the stem cell niche.
abstract: In the adult mammalian body, self-renewal of tissue stem cells is regulated by extracellular niche environments in response to the demands of tissue organization. Intestinal stem cells expressing Lgr5 constantly self-renew in their specific niche at the crypt bottom to maintain rapid turnover of the epithelium. Niche-regulated stem cell self-renewal is perturbed in several mouse genetic models and during human tumorigenesis, suggesting roles for EGF, Wnt, BMP/TGF-β, and Notch signaling. In vitro niche reconstitution capitalizing on this knowledge has enabled the growth of single intestinal stem cells into mini-gut epithelial organoids comprising Lgr5(+) stem cells and all types of differentiated lineages. The mini-gut organoid culture platform is applicable to various types of digestive tissue epithelium from multiple species. The mechanism of self-renewal in organoids provides novel insights for organogenesis, regenerative medicine, and tumorigenesis of the digestive system.
authors.affiliation: Department of Gastroenterology, Keio University School of Medicine, Tokyo 108-8345, Japan; email: t.sato@a7.keio.jp.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Date
authors.affiliation: Department of Gastroenterology, Keio University School of Medicine, Tokyo 108-8345, Japan; email: t.sato@a7.keio.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D004848:Epithelium / Q000502:physiology; D006801:Humans; D007422:Intestines / Q000502:physiology*; D009940:Organoids / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
keywords: cancer; intestine; liver; niche; organoids; pancreas; stem cells; stomach