Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.

Aoki R, Shoshkes-Carmel M, Gao N, Shin S, May CL, Golson ML, Zahm AM, Ray M, Wiser CL, Wright CV, Kaestner KH
Cell Mol Gastroenterol Hepatol. 2016 2 (2): 175-188

PMID: 26949732 · PMCID: PMC4772878 · DOI:10.1016/j.jcmgh.2015.12.004

BACKGROUND & AIMS - Intestinal epithelial stem cells that express Lgr5 and/or 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 maintenance of functional stem cells. Here, we demonstrate definitively that a small subset of mesenchymal, subepithelial cells expressing the winged-helix transcription factor Foxl1 are a critical component of the intestinal stem cell niche.

METHODS - We genetically ablated Foxl1 mesenchymal cells in adult mice using two separate models by expressing either the human or simian diphtheria toxin receptor (DTR) 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.

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