title: Myoblast-derived neuronal cells form glutamatergic neurons in the mouse cerebellum.
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.
authors.affiliation: Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. vgopalak@mdanderson.org
authors.forename: Vidya
authors.initials: V
authors.lastname: Gopalakrishnan
authors.forename: Bihua
authors.initials: B
authors.lastname: Bie
authors.forename: Neeta D
authors.initials: ND
authors.lastname: Sinnappah-Kang
authors.forename: Henry
authors.initials: H
authors.lastname: Adams
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: Zhizhong Z
authors.initials: ZZ
authors.lastname: Pan
authors.forename: Sadhan
authors.initials: S
authors.lastname: Majumder
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002531:Cerebellum / Q000166:cytology*; D058969:Contactin 2 / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002135:Calcium-Binding Proteins; D058969:Contactin 2; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D050777:Stathmin; D014404:Tubulin; D000099229:RE1-Silencing Transcription Factor; C512849:Stmn2 protein, mouse
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