title: Gene expression analysis of laminin-1-induced neurite outgrowth in human mesenchymal stem cells derived from bone marrow.
abstract: 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 differential regulation of 267 genes (>1.5 fold, p < 0.05), predominantly in the category of nervous system development and affected the pathways involved in TGF-β/TNF-α signaling, regulation 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 differentially expressed genes and identified Disrupted in schizophrenia 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-κB inhibitor A (NFκBIA). Collectively, our findings provide the basis for understanding the molecular mechanisms associated with laminin-1-induced neurogenic expression in MSCs.
authors.affiliation: National centre for Cell Science (NCCS), University of Pune, Ganeshkhind, Pune, 411007, India.
authors.forename: S
authors.initials: S
authors.lastname: Mruthyunjaya
authors.forename: D
authors.initials: D
authors.lastname: Parveen
authors.forename: Reecha D
authors.initials: RD
authors.lastname: Shah
authors.forename: Rumma
authors.initials: R
authors.lastname: Manchanda
authors.forename: Ravibhushan
authors.initials: R
authors.lastname: Godbole
authors.forename: Madavan
authors.initials: M
authors.lastname: Vasudevan
authors.forename: Padma
authors.initials: P
authors.lastname: Shastry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007797:Laminin / Q000096:biosynthesis*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016501:Neurites / Q000378:metabolism*
chemical_list: D007797:Laminin; D009419:Nerve Tissue Proteins; C121346:laminin 1
keywords: gene expression; laminin-1; mesenchymal stem cells; neurite