title: Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.
abstract: OBJECTIVE
  Intestinal epithelial stem cells that express Lgr5 and/or Bmi1 continuously replicate and generate differentiated cells throughout life1. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells2. However, ablating Paneth cells has no effect on maintenance of functional stem cells3-5. 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.
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Reina
authors.initials: R
authors.lastname: Aoki
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Shoshkes-Carmel
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Soona
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: May
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Golson
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zahm
authors.affiliation: Vanderbilt University Program in Developmental Biology, Vanderbilt Center for Stem Cell Biology, Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ray
authors.affiliation: Vanderbilt University Program in Developmental Biology, Vanderbilt Center for Stem Cell Biology, Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Wiser
authors.affiliation: Vanderbilt University Program in Developmental Biology, Vanderbilt Center for Stem Cell Biology, Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.affiliation: Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
keywords: Intestinal stem cell niche; Wnt; mesenchyme