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 language | English |
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Pages (from-to) | 269-289 |
Number of pages | 21 |
Journal | Annual Review of Cell and Developmental Biology |
Volume | 31 |
DOIs | |
Publication status | Published - 2015 Nov 13 |
Keywords
- Cancer
- Intestine
- Liver
- Niche
- Organoids
- Pancreas
- Stem cells
- Stomach
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology