Stem cells marked by the R-spondin receptor LGR5

Since the discovery of LGR5 as a marker of intestinal stem cells, the field has developed explosively and led to many new avenues of research. The inner workings of the intestinal crypt stem cell niche are now well understood. The study of stem cell-enriched genes has uncovered some previously unknown aspects of the Wnt signaling pathway, the major driver of crypt dynamics. LGR5(+) stem cells can now be cultured over long periods in vitro as epithelial organoids or "mini-guts." This technology opens new possibilities of using cultured adult stem cells for drug development, disease modeling, gene therapy, and regenerative medicine. This review describes the rediscovery of crypt base columnar cells as LGR5(+) adult stem cells and summarizes subsequent progress, promises, unresolved issues, and challenges of the field.