Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
ISSN: 2157-7013
Vidya Gopalakrishnan, Bihua Bie, Neeta D. Sinnappah-Kang, Henry Adams, Gregory N. Fuller Zhizhong Z. Pan and Sadhan Majumder
Scientific Tracks Abstracts: J Cell Sci Ther
Manipulating cellular plasticity is important for regenerative medicine. We had previously demonstrated that myoblasts could be directed to assume a physiologically active neuronal phe- notype by expressing a single recombinant transcription factor, REST-VP16. Th is activated the expression of neuronal diff erentiation genes that were targets of the repressive activity of the RE1 Silencing Transcription Factor (REST). However, the subtype of neurons generated and their ability to establish synaptic communication in the brain were not known. Here, we show that myoblasts engineered to express green fl uorescent protein and REST-VP16 (M-RV-GFP) exhibited functional ion channels but lacked synaptic communication in vitro . However, trans- plantation of M-RV-GFP cells into the cerebella of newborn mice, a site of extensive postnatal neurogenesis, facilitated their diff erentiation into granule neuron-like cells that expressed tran- sient axonal glycoprotein-1, neurofi lament, type-III b-tubulin, superior cervical ganglia-clone 10, glutamate receptor-2, and glutamate decarboxylase. M-RV-GFP neurons also exhibited ac- tion potentials and received synaptic input that could be blocked by inhibitors of NMDA and non-NMDA type glutamate receptors, suggesting that the transplanted REST-VP16 expressing cells had diff erentiated into glutamatergic neurons. Th is is an important neuronal subtype, in the postnatal cerebellar milieu. In contrast, control myoblasts diff erentiated into myotubes in- dicating that both REST-dependent cell-intrinsic signaling as well as cell-extrinsic factors were important for reprogramming gene expression and directing neuronal subtype specifi city in the brain microenvironment.
Dr. Gopalakrishnan completed her Ph.D from the University of Pittsburgh and her postdoctoral studies from Johns Hopkins University School of Medicine. She is currently an Assistant Professor of Pediatrics and Molecular and Cellular Oncology at the University of Texas MD Anderson Cancer Center. Her research is focused on developing mouse models for pediatric brain tumors, identifying novel molecules for targeted therapeutics and manipulating lineage speci fi cation in stem cells for neuro-regeneration. She has a number of publications in high impact peer-reviewed journals.