The CSF-1 receptor fashions the intestinal stem cell niche

Stem Cell Res. 2013 Mar;10(2):203-12. doi: 10.1016/j.scr.2012.12.001. Epub 2012 Dec 9.


Gastrointestinal (GI) homeostasis requires the action of multiple pathways. There is some controversy regarding whether small intestine (SI) Paneth cells (PCs) 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) knock out (KO) or Csf1 mutation is 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 a high resolution 3D localization of CSF-1R mainly to PC. The induction of GI-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, changed distribution of proliferating cells and this was with a commensurate loss of Lgr5 and other stem cell marker gene expression. 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. These results show that CSF-1R directly supports PC maturation and that in turn PCs fashion the intestinal stem cell niche.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD24 Antigen / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Intestine, Small / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Specificity / genetics
  • Organoids / cytology
  • Organoids / metabolism
  • Paneth Cells / cytology
  • Paneth Cells / metabolism
  • Receptor, Macrophage Colony-Stimulating Factor / deficiency
  • Receptor, Macrophage Colony-Stimulating Factor / genetics
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism*
  • Receptors, Notch / metabolism
  • Stem Cell Niche* / genetics
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Wnt Proteins / metabolism


  • CD24 Antigen
  • Receptors, Notch
  • Wnt Proteins
  • Receptor, Macrophage Colony-Stimulating Factor