Inhibition of GSK-3β enhances neural differentiation in unrestricted somatic stem cells

Cell Biol Int. 2012 Nov 1;36(11):967-72. doi: 10.1042/CBI20110541.

Abstract

GSK-3β is a key molecule in several signalling pathways, including the Wnt/β-catenin signalling pathway. There is increasing evidence suggesting Wnt/β-catenin signalling is involved in the neural differentiation of embryonic, somatic and neural stem cells. However, a large body of evidence indicates that this pathway maintains stem cells in a proliferative state. To address this controversy, we have investigated whether the Wnt/β-catenin pathway is present and involved in the neural differentiation of newly introduced USSCs (unrestricted somatic stem cells). Our results indicate that the components of Wnt/β-catenin signalling are present in undifferentiated USSCs. We also show that the treatment of neurally induced USSCs with BIO (6-bromoindirubin-3'-oxime), a specific GSK-3β inhibitor and Wnt activator, for 5 and 10 days results in increased expression of a general neuronal marker (β-tubulin III). Moreover, the expression of pGSK-3β and stabilized β-catenin increased by BIO in neurally induced USSCs, indicates that the Wnt pathway is activated and functional in these cells. Thus, inhibition of GSK-3β in USSCs enhances their neural differentiation, which suggests a positive role of the Wnt/β-catenin signalling pathway towards neural fate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Active Transport, Cell Nucleus
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Fetal Blood / cytology
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Immunohistochemistry
  • Indoles / pharmacology
  • Neurogenesis*
  • Oximes / pharmacology
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Time Factors
  • Tretinoin / pharmacology
  • Tubulin / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • 6-bromoindirubin-3'-oxime
  • CTNNB1 protein, human
  • Indoles
  • Oximes
  • TUBB3 protein, human
  • Tubulin
  • beta Catenin
  • Tretinoin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • 1-Methyl-3-isobutylxanthine