title: Role of lipid rafts in neuronal differentiation of dental pulp-derived stem cells.
abstract: Human dental pulp-derived stem cells (hDPSCs) are characterized by a typical fibroblast-like morphology. They express specific markers for mesenchymal stem cells and are capable of differentiation into osteoblasts, adipoblasts and neurons in vitro. Previous studies showed that gangliosides are involved in the induction of early neuronal differentiation of hDPSCs. This study was undertaken to investigate the role of lipid rafts in this process. Lipid rafts are signaling microdomains enriched in glycosphingolipids, cholesterol, tyrosine kinase receptors, mono- or heterotrimeric G proteins and GPI-anchored proteins. We preliminary showed that established cells expressed multipotent mesenchymal stromal-specific surface antigens. Then, we analyzed the distribution of lipid rafts, revealing plasma membrane microdomains with GM2 and EGF-R enrichment. Following stimulation with EGF/bFGF, neuronal differentiation was observed. To analyze the functional role of lipid rafts in EGF/bFGF-induced hDPSCs differentiation, cells were preincubated with lipid raft affecting agents, i.e. [D]-PDMP or methyl-β-cyclodextrin. These compounds significantly prevented neuronal-specific antigen expression, as well as Akt and ERK 1/2 phosphorylation, induced by EGF/bFGF, indicating that lipid raft integrity is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that lipid rafts may represent specific chambers, where multimolecular signaling complexes, including lipids (gangliosides, cholesterol) and proteins (EGF-R), play a role in hDPSCs differentiation.
authors.affiliation: Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mattei
authors.affiliation: Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy.
authors.forename: Costantino
authors.initials: C
authors.lastname: Santacroce
authors.affiliation: Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tasciotti
authors.affiliation: Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Martellucci
authors.affiliation: Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, viale Regina Elena 324, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Manganelli
authors.affiliation: Department of Science dentistry and maxillofacial, "Sapienza" University, viale Regina Elena, 287/A, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Piccoli
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, viale Regina Elena 324, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Misasi
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, viale Regina Elena 324, Rome, Italy; Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy. Electronic address: maurizio.sorice@uniroma1.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, viale Regina Elena 324, Rome, Italy.
authors.forename: Tina
authors.initials: T
authors.lastname: Garofalo
mesh_terms: D002454:Cell Differentiation; D003782:Dental Pulp / Q000166:cytology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism
keywords: Dental pulp-derived stem cells; Gangliosides; Lipid rafts; Microdomains; Neuronal differentiation