Cellular and Molecular Gastroenterology and Hepatology (Mar 2016)

Foxl1-Expressing Mesenchymal Cells Constitute the Intestinal Stem Cell NicheSummary

  • Reina Aoki,
  • Michal Shoshkes-Carmel,
  • Nan Gao,
  • Soona Shin,
  • Catherine L. May,
  • Maria L. Golson,
  • Adam M. Zahm,
  • Michael Ray,
  • Caroline L. Wiser,
  • Christopher V.E. Wright,
  • Klaus H. Kaestner

Journal volume & issue
Vol. 2, no. 2
pp. 175 – 188

Abstract

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Background & Aims: Intestinal epithelial stem cells that express leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) and/or B cell specific Moloney murine leukemia virus integration site 1 (Bmi1) continuously replicate and generate differentiated cells throughout life. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells. However, ablating Paneth cells has no effect on the maintenance of functional stem cells. Here, we show definitively that a small subset of mesenchymal subepithelial cells expressing the winged-helix transcription factor forkhead box l1 (Foxl1) are a critical component of the intestinal stem cell niche. Methods: We genetically ablated Foxl1+ mesenchymal cells in adult mice using 2 separate models by expressing either the human or simian diphtheria toxin receptor under Foxl1 promoter control. Conclusions: Killing Foxl1+ cells by diphtheria toxin administration led to an abrupt cessation of proliferation of both epithelial stem- and transit-amplifying progenitor cell populations that was associated with a loss of active Wnt signaling to the intestinal epithelium. Therefore, Foxl1-expressing mesenchymal cells constitute the fundamental niche for intestinal stem cells. Keywords: Intestinal Stem Cell Niche, Wnt, Mesenchyme