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

Author

Listed:
  • Salvatore Simmini

    (Hubrecht Institute and UMC Utrecht)

  • Monika Bialecka

    (Hubrecht Institute and UMC Utrecht
    Present address: University of Cambridge, Department of Physiology, Development & Neuroscience and Gurdon Institute Downing Street, Cambridge CB2 3DY, UK)

  • Meritxell Huch

    (Hubrecht Institute and UMC Utrecht
    Present address: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK)

  • Lennart Kester

    (Hubrecht Institute and UMC Utrecht)

  • Marc van de Wetering

    (Hubrecht Institute and UMC Utrecht)

  • Toshiro Sato

    (Hubrecht Institute and UMC Utrecht
    Present address: Department of Gastroenterology, School of Medicine, Keio University Tokyo, Japan)

  • 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)

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.

Suggested Citation

  • Salvatore Simmini & Monika Bialecka & Meritxell Huch & Lennart Kester & Marc van de Wetering & Toshiro Sato & Felix Beck & Alexander van Oudenaarden & Hans Clevers & Jacqueline Deschamps, 2014. "Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6728
    DOI: 10.1038/ncomms6728
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    Cited by:

    1. Kathleen Shah & Muralidhara Rao Maradana & M. Joaquina Delàs & Amina Metidji & Frederike Graelmann & Miriam Llorian & Probir Chakravarty & Ying Li & Mauro Tolaini & Michael Shapiro & Gavin Kelly & Chr, 2022. "Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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