TY - JOUR
T1 - Myoblast-derived neuronal cells form glutamatergic neurons in the mouse cerebellum
AU - Gopalakrishnan, Vidya
AU - Bie, Bihua
AU - Sinnappah-Kang, Neeta D.
AU - Adams, Henry
AU - Fuller, Gregory N.
AU - Pan, Zhizhong Z.
AU - Majumder, Sadhan
PY - 2010/10
Y1 - 2010/10
N2 - Production of neurons from non-neural cells has farreaching 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.
AB - Production of neurons from non-neural cells has farreaching 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.
KW - Cerebellum
KW - Glutamatergic neurons
KW - Myoblasts
KW - REST
KW - REST-VP16
UR - http://www.scopus.com/inward/record.url?scp=78149314597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149314597&partnerID=8YFLogxK
U2 - 10.1002/stem.509
DO - 10.1002/stem.509
M3 - Article
C2 - 20799335
AN - SCOPUS:78149314597
SN - 1066-5099
VL - 28
SP - 1839
EP - 1847
JO - STEM CELLS
JF - STEM CELLS
IS - 10
ER -