Transient Expression of WNT2 Promotes Somatic Cell Reprogramming by Inducing β-Catenin Nuclear Accumulation

Stem Cell Reports. 2016 Jun 14;6(6):834-843. doi: 10.1016/j.stemcr.2016.04.012. Epub 2016 May 19.

Abstract

Treatment with several Wnt/β-catenin signaling pathway regulators can change the cellular reprogramming efficiency; however, the dynamics and role of endogenous Wnt/β-catenin signaling in reprogramming remain largely unanswered. Here we identify the upregulation of WNT2 and subsequent β-catenin nuclear accumulation as key events in reprogramming. Transient nuclear accumulation of β-catenin occurs early in MEF reprogramming. Wnt2 is strongly expressed in the early stage of reprogramming. Wnt2 knockdown suppresses the nuclear accumulation of β-catenin and reduces the reprogramming efficiency. WNT2 overexpression promotes β-catenin nuclear accumulation and enhances the reprogramming efficiency. WNT2 contributes to the promotion of cell proliferation. Experiments with several drugs that control the Wnt pathway also indicate the importance of β-catenin nuclear accumulation in reprogramming. Our findings reveal the role of WNT2/β-catenin signaling in reprogramming.

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Proliferation
  • Cellular Reprogramming*
  • Embryo, Mammalian
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Thy-1 Antigens / genetics
  • Thy-1 Antigens / metabolism
  • Wnt2 Protein / genetics*
  • Wnt2 Protein / metabolism
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • Cadherins
  • Cdh1 protein, mouse
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Thy-1 Antigens
  • Wnt2 Protein
  • beta Catenin