The CSF-1 receptor fashions the intestinal stem cell niche

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalStem Cell Research
Volume10
Issue number2
DOIs
StatePublished - Mar 2013
Externally publishedYes

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Macrophage Colony-Stimulating Factor Receptors
Paneth Cells
Stem Cell Niche
Stem Cells
Small Intestine
Organoids
Gene Expression
Young Adult
Homeostasis
Epithelial Cells
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Akcora, D., Huynh, D., Lightowler, S., Germann, M., Robine, S., de May, J. R., ... Ramsay, R. G. (2013). The CSF-1 receptor fashions the intestinal stem cell niche. Stem Cell Research, 10(2), 203-212. https://doi.org/10.1016/j.scr.2012.12.001

The CSF-1 receptor fashions the intestinal stem cell niche. / Akcora, Dilara; Huynh, Duy; Lightowler, Sally; Germann, Markus; Robine, Sylvie; de May, Jan R.; Pollard, Jeffrey W.; Stanley, E. Richard; Malaterre, Jordane; Ramsay, Robert G.

In: Stem Cell Research, Vol. 10, No. 2, 03.2013, p. 203-212.

Research output: Contribution to journalArticle

Akcora, D, Huynh, D, Lightowler, S, Germann, M, Robine, S, de May, JR, Pollard, JW, Stanley, ER, Malaterre, J & Ramsay, RG 2013, 'The CSF-1 receptor fashions the intestinal stem cell niche', Stem Cell Research, vol. 10, no. 2, pp. 203-212. https://doi.org/10.1016/j.scr.2012.12.001
Akcora D, Huynh D, Lightowler S, Germann M, Robine S, de May JR et al. The CSF-1 receptor fashions the intestinal stem cell niche. Stem Cell Research. 2013 Mar;10(2):203-212. https://doi.org/10.1016/j.scr.2012.12.001
Akcora, Dilara ; Huynh, Duy ; Lightowler, Sally ; Germann, Markus ; Robine, Sylvie ; de May, Jan R. ; Pollard, Jeffrey W. ; Stanley, E. Richard ; Malaterre, Jordane ; Ramsay, Robert G. / The CSF-1 receptor fashions the intestinal stem cell niche. In: Stem Cell Research. 2013 ; Vol. 10, No. 2. pp. 203-212.
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