Sadhan Majumder, Vidya Gopalakrishnan, Bihua Bie, Neeta D Sinnappah-Kang, Henry Adams, Gregory N Fuller and Zhizhong Z Pan
Scientific Tracks Abstracts: J Stem Cell Res Ther
Productions of neuros from non-neural cells have far-reaching clinical significance. We previously found that muscle progenitor cells
(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.