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

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.

Afiliación

Akcora D; Peter MacCallum Cancer Centre and the Sir Peter MacCallum Oncology Department, University of Melbourne, Australia.

Stem Cell Res ; 10(2): 203-12, 2013 Mar.

Article en En | MEDLINE | ID: mdl-23314290

RESUMEN

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.

Asunto(s)

Intestino Delgado/citología; Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo; Nicho de Células Madre; Células Madre/citología; Células Madre/metabolismo; Animales; Antígeno CD24/metabolismo; Diferenciación Celular/genética; Proliferación Celular; Eliminación de Gen; Perfilación de la Expresión Génica; Regulación de la Expresión Génica; Ratones; Ratones Endogámicos C57BL; Ratones Noqueados; Especificidad de Órganos/genética; Organoides/citología; Organoides/metabolismo; Células de Paneth/citología; Células de Paneth/metabolismo; Receptor de Factor Estimulante de Colonias de Macrófagos/deficiencia; Receptor de Factor Estimulante de Colonias de Macrófagos/genética; Receptores Notch/metabolismo; Nicho de Células Madre/genética; Proteínas Wnt/metabolismo

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Receptor de Factor Estimulante de Colonias de Macrófagos / Nicho de Células Madre / Intestino Delgado Límite: Animals Idioma: En Revista: Stem Cell Res Año: 2013 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido

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