Foxl1-Expressing Mesenchymal Cells Constitute the Intestinal Stem Cell Niche

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)175-188
Number of pages14
JournalCMGH
Volume2
Issue number2
DOIs
StatePublished - 1 Feb 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 The Authors.

Keywords

  • Intestinal Stem Cell Niche
  • Mesenchyme
  • Wnt

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