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Article first published online: 26 OCT 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 10, pages 1839–1847, October 2010
How to Cite
Gopalakrishnan, V., Bie, B., Sinnappah-Kang, N. D., Adams, H., Fuller, G. N., Pan, Z. Z. and Majumder, S. (2010), Myoblast-Derived Neuronal Cells Form Glutamatergic Neurons in the Mouse Cerebellum. STEM CELLS, 28: 1839–1847. doi: 10.1002/stem.509
Author contributions: V.G., Z.Z.P., and S. M.: conception and design, financial support, collection, interpretation and assembly of data, manuscript writing; B.B., N.D.S.-K., H.A., and G.N.F.: collection, interpretation and assembly of data.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS August 26, 2010.
- Issue published online: 26 OCT 2010
- Article first published online: 26 OCT 2010
- Accepted manuscript online: 26 AUG 2010 12:00AM EST
- Manuscript Accepted: 18 AUG 2010
- Manuscript Received: 18 MAY 2010
- Glutamatergic neurons;
Production of neurons from non-neural cells has far-reaching clinical significance. We previously found that myoblasts can be converted to a physiologically active neuronal phenotype by transferring a single recombinant transcription factor, REST-VP16, which directly activates target genes of the transcriptional repressor, REST. However, the neuronal subtype of M-RV cells and whether they can establish synaptic communication in the brain have remained unknown. M-RV cells engineered to express green fluorescent protein (M-RV-GFP) had functional ion channels but did not establish synaptic communication in vitro. However, when transplanted into newborn mice cerebella, a site of extensive postnatal neurogenesis, these cells expressed endogenous cerebellar granule precursors and neuron proteins, such as transient axonal glycoprotein-1, neurofilament, type-III β-tubulin, superior cervical ganglia-clone 10, glutamate receptor-2, and glutamate decarboxylase. Importantly, they exhibited action potentials and were capable of receiving glutamatergic synaptic input, similar to the native cerebellar granule neurons. These results suggest that M-RV-GFP cells differentiate into glutamatergic neurons, an important neuronal subtype, in the postnatal cerebellar milieu. Our findings suggest that although activation of REST-target genes can reprogram myoblasts to assume a general neuronal phenotype, the subtype specificity may then be directed by the brain microenvironment. STEM CELLS 2010;28:1839–1847