Oral Presentation 6th Australian Health and Medical Research Congress 2012

The CSF-1 Receptor Fashions the Intestinal Stem Cell Niche (#147)

Dilara Akcora 1 , Duy Huynh 1 , Sally Lightowler 1 , Sylvie Robine 2 , Jan R. de May 3 4 , Jeffrey W. Pollard 5 , E. Richard Stanley 5 , Jordane Malaterre 1 , Robert G. Ramsay 1
  1. Peter MacCallum Cancer Centre and the Sir Peter MacCallum Oncology Department and the Pathology Department, University Of Melbourne , Melbourne, VIC, Australia
  2. Centre National de la Recherche Scientifique, Institut Curie, Paris, France
  3. Laboratoire de Biophotonique et Pharmacologie, CNRS, Illkirch, France
  4. Universite de Strasbourg, Strasbourg, France
  5. Albert Einstein College of Medicine, Bronx, New York, USA

Gastrointestinal (GI) homeostasis requires the action of multiple pathways. There is some controversy regarding whether small intestine (SI) Paneth cells (PC) play a central role in orchestrating crypt architecture and their relationship with Lgr5+ve stem cells. Nevertheless, we previously showed that germline CSF-1 receptor (Csf1r) deletion (KO) or Csf-1 mutation are associated with an absence of mature PC, reduced crypt proliferation and lowered stem cell gene, Lgr5 expression. Here we show the additional loss of CD24, Bmi1 and olfm4 expression in the KO crypts and using high resolution 3D microscopy confirm localization of CSF1R mainly to PC.  By culturing SI organoids, we further show that the Csf1r-/- defect in PC production is intrinsic to epithelial cells as well as definitively affecting stem cell activity. Induction of gastro-intestinal-specific Csf1r deletion in young adult mice also led to PC loss over a period of weeks, in accord with the anticipated long life span of PC, and this was with a commensurate loss of Lgr5 and other stem cell marker gene expression.  These results show that CSF-1R directly supports PC maturation and that in turn PCs fashion the intestinal stem cell niche.