Beta-catenin signalling in mesenchymal islet-derived precursor cells

Cell Prolif. 2008 Jun;41(3):474-91. doi: 10.1111/j.1365-2184.2008.00527.x. Epub 2008 Apr 14.


Objectives: Previously, we characterized human islet-derived precursor cells (hIPCs) as mesenchymal stem cells that migrate out from islets in vitro and can differentiate into functional islet-like structures following proliferative expansion. Here, we investigate the role of beta-catenin signalling in derivation and proliferation of hIPCs.

Materials and methods: Localization of beta-catenin was performed using confocal microscopy. Expression levels of beta-catenin target genes were measured by quantitative real-time polymerase chain reaction. Loss-of-function studies were performed using specific short interfering RNAs.

Results: Immunostaining of islet outgrowths revealed translocation of beta-catenin from plasma membranes in intact islets to the nucleus in cells migrating out. There were no nuclear beta-catenin-positive cells in intact islets whereas between 35% and 70% of cells in established hIPC cultures exhibited nuclear beta-catenin. Transcripts for beta-catenin target genes were increased in hIPCs compared to those in islets. Beta-catenin translocated to the cell membrane when hIPCs formed epithelial cell clusters. In proliferating hIPCs, there was a strong correlation between markers of proliferation and nuclear beta-catenin. Treatment of hIPCs with the glycogen synthase kinase-3beta inhibitor (2'Z,3'E)-6-Bromoindirubin-3'-oxime increased intracellular beta-catenin but reduced nuclear beta-catenin, and was associated with reduced cell proliferation. Finally, knockdown of beta-catenin decreased beta-catenin target gene expression and hIPC proliferation.

Conclusions: These results support a functional role for beta-catenin during proliferation of hIPCs and suggest that activated beta-catenin signalling may also be important during hIPC derivation from islets.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Biomarkers / metabolism
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Epithelium / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism*
  • Mesoderm / cytology*
  • Mesoderm / metabolism
  • Protein Transport
  • Signal Transduction*
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Transcription, Genetic
  • Wnt Proteins / genetics
  • beta Catenin / metabolism*


  • Biomarkers
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Wnt Proteins
  • beta Catenin