Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts

Nature. 2011 Jan 20;469(7330):415-8. doi: 10.1038/nature09637. Epub 2010 Nov 28.

Abstract

Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins. Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt-villus organoids in the absence of non-epithelial niche cells. Here we find a close physical association of Lgr5 stem cells with Paneth cells in mice, both in vivo and in vitro. CD24(+) Paneth cells express EGF, TGF-α, Wnt3 and the Notch ligand Dll4, all essential signals for stem-cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation. This Paneth cell requirement can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, CD24(+) cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell.

MeSH terms

  • Animals
  • CD24 Antigen / metabolism
  • Cell Count
  • Cell Proliferation
  • Coculture Techniques
  • Humans
  • Intestines / cytology*
  • Mice
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / metabolism*
  • Paneth Cells / cytology*
  • Paneth Cells / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Stem Cell Niche / cytology*
  • Stem Cell Niche / metabolism
  • Wnt Proteins / metabolism
  • Wnt3 Protein

Substances

  • CD24 Antigen
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • WNT3 protein, human
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3 protein, mouse

Associated data

  • GEO/GSE25109