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Conversion of myoblasts to physiologically active neuronal phenotype.
Yumi Watanabe1, Sei Kameoka, Vidya Gopalakrishnan
1Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Genes & Development
|April 14, 2004
Summary
Expressing REST-VP16 in myoblasts converted them to functional neurons, overriding muscle differentiation. This single transgene approach efficiently triggers neuronal differentiation in stem cells.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Molecular Biology
Background:
- Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) normally represses neuronal differentiation genes.
- REST-VP16 activates REST/NRSF target genes, but its ability to induce neuronal formation from stem cells was unknown.
Purpose of the Study:
- To investigate if REST-VP16 expression is sufficient to induce neuronal differentiation from myoblasts.
- To determine if REST-VP16 can override existing differentiation pathways.
Main Methods:
- Myoblasts were cultured under muscle differentiation conditions with REST-VP16 expression.
- Neuronal differentiation markers and physiological activity were assessed.
- In vitro differentiated neurons were transplanted into mouse brains.
Main Results:
- REST-VP16 expression blocked muscle differentiation and activated neuronal genes in myoblasts.
- Myoblasts were converted to a physiologically active neuronal phenotype.
- Transplanted neurons survived, integrated into the brain, and did not form tumors.
Conclusions:
- A single transgene, REST-VP16, is sufficient to trigger neuronal differentiation in myoblasts by activating target genes and overriding muscle differentiation.
- This method offers an efficient strategy for inducing neuronal differentiation in myoblasts and potentially other stem cells.
- REST-VP16-derived neurons are suitable for transplantation and integration into the brain.