Global gene profiling utilizing a cell model of spinal muscular atrophy

Maeda, Miho
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University of Delaware
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by mutations in the survival motor neuron gene (SMN). Despite understanding the genetic basis behind the diseases, questions still remain about the specificity of the disease; why are motor neurons selectively affected? Using a mouse embryonic stem (mES) cell model for severe SMA, our present study had two aims. The first aim was to differentiate ES cells into motor neurons (MNs) and to characterize the differentiated cells to test their identity. The second aim was to isolate RNA from the ES cell derived MNs and to study their gene expression pattern through next generation sequencing technology (RNA-Seq). Our results have found that the ES cells from a severe SMA mouse model can be induced to generate MNs. When the transcriptome of SMA cells were compared to control cells, we found distinct gene expression patterns. Pluripotency and cell proliferation markers were increased significantly in SMA cells, whereas control cells had higher expression in neuronal development markers. Taken together, our study suggests an overall reduction in MN differentiation in this specific mES cell model of SMA. These findings suggest that SMN reduction in mES cells affects processes critical for normal development and maintenance in motor neurons.