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The CSF-1 receptor fashions the intestinal stem cell niche

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  • Dilara Akcora
  • Duy Huynh
  • Sally Lightowler
  • Markus Germann
  • Sylvie Robine
  • Jan R de May
  • Jeffrey W Pollard
  • E Richard Stanley
  • Jordane Malaterre
  • Robert G Ramsay

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    Rights statement: Published in final edited form as: Stem Cell Res. Mar 2013; 10(2): 203–212.

    Accepted author manuscript, 2.98 MB, PDF document

http://www.sciencedirect.com/science/article/pii/S1873506112001237
Original languageEnglish
Pages (from-to)203-12
Number of pages10
JournalStem cell research
Volume10
Issue number2
DOIs
Publication statusPublished - Mar 2013

Abstract

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.

    Research areas

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

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