Abstract
The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene repertoire that they express. Both types of stem cells have been shown to grow from single cells into 3D structures (organoids) in vitro. We show that single adult Lgr5-positive stem cells, isolated from small intestinal organoids, require Cdx2 to maintain their intestinal identity and are converted cell-autonomously into pyloric stem cells in the absence of this transcription factor. Clonal descendants of Cdx2null small intestinal stem cells enter the gastric differentiation program instead of producing intestinal derivatives. We show that the intestinal genetic programme is critically dependent on the single transcription factor encoding gene Cdx2.
Highlights
The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium
We find that the properties and transcriptional signature of adult Small intestinal stem cells (SI stem cell (SC)) cultured in vitro as organoids are critically dependent on the expression of the transcription factor Cdx[2]
It had been found that inactivation of the intestinal-specific transcription factor Cdx[2] in the adult mouse intestinal epithelium leads to the transformation of some of the crypts into submucosal empty cysts expressing stomach markers[6,7]
Summary
The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene repertoire that they express Both types of stem cells have been shown to grow from single cells into 3D structures (organoids) in vitro. We show that single SI SCs wherein Cdx[2] was inactivated rapidly lose their intestinal identity and acquire a gastric pyloric identity They cannot give rise to intestinal organoids in vitro as their wild-type counterparts do, and instead manifest growth properties and transcriptional profile of gastric pyloric SCs. Cdx2null SI SCs exclusively express the transcriptional programme of gastric pyloric stem cells and generate differentiated derivatives of all pyloric lineages. These data indicate that Cdx[2] is a major determinant of the identity and fate of adult small intestinal stem cells
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