Transformation of Intestinal Stem Cells Into Gastric Stem Cells on Loss of Transcription Factor Cdx2

Nat Commun. 2014 Dec 11;5:5728. doi: 10.1038/ncomms6728.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDX2 Transcription Factor
  • Cell Culture Techniques
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cellular Reprogramming / genetics*
  • Female
  • Gastric Mucosa / cytology
  • Gastric Mucosa / metabolism*
  • Homeodomain Proteins / genetics*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / cytology
  • Intestine, Small / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcriptome

Substances

  • CDX2 Transcription Factor
  • Cdx2 protein, mouse
  • Homeodomain Proteins
  • Transcription Factors

Associated data

  • GEO/GSE51751
  • GEO/GSE62784