TY - JOUR
T1 - Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2
AU - Simmini, Salvatore
AU - Bialecka, Monika
AU - Huch, Meritxell
AU - Kester, Lennart
AU - Van De Wetering, Marc
AU - Sato, Toshiro
AU - Beck, Felix
AU - Van Oudenaarden, Alexander
AU - Clevers, Hans
AU - Deschamps, Jacqueline
N1 - Funding Information:
We thank Stieneke van den Brink for help with the organoid culture facility and Harry Begthel and Jeroen Korving for help in histology. We acknowledge the Hubrecht Imaging Center, and Edwin Cuppen and Ewart de Bruijn of the Utrecht Sequencing Facility for next-generation sequencing. We also thank Henner Farin for providing us with his lentiviral construct, and Peter van Sluis and Richard Volckmann from the AMC (UvA, Amsterdam, the Netherlands) for their help with the Affymetrix microarray analysis. We thank Roel Neijts and Shilu Amin for reading the manuscript. This work was supported by a grant from the Dutch Earth and Life sciences (NWO ALW 820.02.005) and a grant from the Dutch government to the Netherlands Institute for Regenerative Medicine (NIRM grant FES0908).
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014
Y1 - 2014
N2 - 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 Cdx2 null 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.
AB - 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 Cdx2 null 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.
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U2 - 10.1038/ncomms6728
DO - 10.1038/ncomms6728
M3 - Article
C2 - 25500896
AN - SCOPUS:84923309602
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 5728
ER -