(786f) Signal Transduction of the Physical Environment in the Neural Differentiation of Stem Cells

Neural differentiation is largely dependent on extracellular signals within the cell microenvironment. These extracellular signals are mainly in the form of soluble factors that activate intracellular signaling cascades that drive changes in the cell nucleus. However, it is becoming increasingly apparent that the physical microenvironment provides signals that can also influence lineage commitment and very low modulus surfaces has been repeatedly demonstrated to promote neurogenesis. The molecular mechanisms governing mechano-induced neural differentiation are still largely uncharacterized; however, a growing body of evidence indicates that physical stimuli can regulate known signaling cascades and transcription factors involved in neural differentiation. Understanding how the physical environment affects neural differentiation at the molecular level will enable research and design of materials that will eventually enhance neural stem cell differentiation, homogeneity, and specificity. Previous findings have shown that the neural phenotype in stem cells is strongly repressed by the Neuron Restrictive Silencer Factor (NRSF). NRSF coordinately represses up to 300 genes involved in neural differentiation. Recently, we found that the neural induction in mesenchymal stem cells (MSCs) by forskolin and IBMX is dependent on the downregulation of NRSF and derepression of its downstream targets. Therefore we set out to determine whether soft surfaces could induce neural phenotype in MSCs also through downregulation of NRSF. Indeed we found that several neural characteristics induced by soft surfaces including increase in neural marker expression (Tuj), biosynthetic enzymes (TH), and neuronal function are repressed by NRSF.