Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2

Salvatore Simmini, Monika Bialecka, Meritxell Huch, Lennart Kester, Marc van de Wetering, Toshiro Sato, Felix Beck, Alexander van Oudenaarden, Hans Clevers and Jacqueline Deschamps ()
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Salvatore Simmini: Hubrecht Institute and UMC Utrecht
Monika Bialecka: Hubrecht Institute and UMC Utrecht
Meritxell Huch: Hubrecht Institute and UMC Utrecht
Lennart Kester: Hubrecht Institute and UMC Utrecht
Marc van de Wetering: Hubrecht Institute and UMC Utrecht
Toshiro Sato: Hubrecht Institute and UMC Utrecht
Felix Beck: University of Leicester
Alexander van Oudenaarden: Hubrecht Institute and UMC Utrecht
Hans Clevers: Hubrecht Institute and UMC Utrecht
Jacqueline Deschamps: Hubrecht Institute and UMC Utrecht

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6728

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