Myoblast-Derived Neuronal Cells Form Glutamatergic Neurons in the Mouse Cerebellum§

Authors

  • Vidya Gopalakrishnan,

    Corresponding author
    1. Departments of Pediatrics,The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
    2. Molecular and Cellular Oncology,The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
    3. Brain Tumor Center, and The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
    4. Programs in Neuroscience and The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA
    • Department of Pediatrics, Unit 853, The University of Texas M. D. Anderson Cancer Center, 1,515 Holcombe Blvd., Houston, Texas 77030, USA
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    • Telephone: 713-792-0498; Fax: 713-563-5407

  • Bihua Bie,

    1. Anesthesiology and Pain Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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  • Neeta D. Sinnappah-Kang,

    1. Departments of Pediatrics,The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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  • Henry Adams,

    1. Molecular and Cellular Oncology,The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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  • Gregory N. Fuller,

    1. Programs in Neuroscience and The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA
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  • Zhizhong Z. Pan,

    1. Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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  • Sadhan Majumder

    Corresponding author
    1. Brain Tumor Center, and The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
    2. Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
    3. Genes and Development, The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA
    • Department of Genetics, Unit 1010, The University of Texas M. D. Anderson Cancer Center, 1,515 Holcombe Blvd., Houston, Texas 77030, USA
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    • Telephone: 713-834-6347; Fax: 713-834-6400


  • 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.

Abstract

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

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