Mini-Gut Organoids: Reconstitution of the Stem Cell Niche

Shoichi Date, Toshiro Sato

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

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, BMPTGF-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.

Original languageEnglish
Pages (from-to)269-289
Number of pages21
JournalAnnual Review of Cell and Developmental Biology
Volume31
DOIs
Publication statusPublished - 2015 Nov 13

Keywords

  • Cancer
  • Intestine
  • Liver
  • Niche
  • Organoids
  • Pancreas
  • Stem cells
  • Stomach

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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