Single Lgr5 Stem Cells Build Crypt-Villus Structures in Vitro Without a Mesenchymal Niche

Nature. 2009 May 14;459(7244):262-5. doi: 10.1038/nature07935. Epub 2009 Mar 29.

Abstract

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5(+) stem cells can also initiate these cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

MeSH terms

  • Animals
  • Cell Culture Techniques / methods*
  • Cell Lineage
  • Cell Separation
  • Gene Expression Regulation, Developmental
  • Intestinal Mucosa / metabolism
  • Intestines / anatomy & histology*
  • Intestines / cytology*
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism
  • Organoids / cytology*
  • Organoids / growth & development
  • Organoids / metabolism
  • Paneth Cells / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Notch / metabolism
  • Regeneration
  • Stem Cell Niche
  • Stem Cells / cytology*
  • Stem Cells / metabolism*

Substances

  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Notch