Gene expression analysis of laminin-1-induced neurite outgrowth in human mesenchymal stem cells derived from bone marrow

The mechanisms underlying the differentiation of Mesenchymal stem cells (MSCs) toward neuronal cell type are not clearly understood. Earlier, we reported that laminin-1 induces neurite outgrowth in human MSCs via c-Jun/AP-1 activation through ERK, JNK, and Akt pathways. In this study, we demonstrate that laminin-1 increases the expression of proneural gene, neuroD1 and induces the expression of immediate-early biomarkers of neuronal cell-programming— Egr1, Egr3, PC3, and PC4. Gene expression profiling of MSCs cultured on laminin-1 and Poly-L-lysine for 12 h revealed dif- ferential regulation of 267 genes (>1.5 fold, p < 0.05), predom- inantly in the category of nervous system development and affected the pathways involved in TGF-b/TNF-a signaling, reg- ulation of MAPK and JNK cascade. Data for 11 selected genes related to nervous system development was validated by real time PCR. Transcriptional regulatory network analysis revealed c-Jun as the key transcription factor regulating majority of dif- ferentially expressed genes and identified Disrupted in schizo- phrenia 1, as a novel target of c-Jun. Modeling and analysis of biological network showed selective induction of Growth Arrest and DNA damage 45 (GADD45B) and repression of NF- jB inhibitor A (NFjBIA). Collectively, our findings provide the basis for understanding the molecular mechanisms associated with laminin-1-induced neurogenic expression in MSCs. V C 2014