title: The CSF-1 receptor fashions the intestinal stem cell niche.
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.
authors: Peter MacCallum Cancer Centre and the Sir Peter MacCallum Oncology Department, University of Melbourne, Australia.
authors: Dilara
authors: D
authors: Akcora
authors: Duy
authors: D
authors: Huynh
authors: Sally
authors: S
authors: Lightowler
authors: Markus
authors: M
authors: Germann
authors: Sylvie
authors: S
authors: Robine
authors: Jan R
authors: JR
authors: de May
authors: Jeffrey W
authors: JW
authors: Pollard
authors: E Richard
authors: ER
authors: Stanley
authors: Jordane
authors: J
authors: Malaterre
authors: Robert G
authors: RG
authors: Ramsay
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D009940:Organoids / Q000166:cytology / Q000378:metabolism; D019879:Paneth Cells / Q000166:cytology / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D055153:Stem Cell Niche / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D051927:CD24 Antigen; D051880:Receptors, Notch; D051153:Wnt Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor