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Annu Rev Cell Dev Biol. 2015;31:269-89. doi: 10.1146/annurev-cellbio-100814-125218. Epub 2015 Oct 2.

Mini-gut organoids: reconstitution of the stem cell niche.

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Department of Gastroenterology, Keio University School of Medicine, Tokyo 108-8345, Japan; email:


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.


cancer; intestine; liver; niche; organoids; pancreas; stem cells; stomach

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