title: Neuronal differentiation of human mesenchymal stem cells: changes in the expression of the Alzheimer's disease-related gene seladin-1.
abstract: Seladin-1 (SELective Alzheimer's Disease INdicator-1) is an anti-apoptotic gene, which is down-regulated in brain regions affected by Alzheimer's disease (AD). In addition, seladin-1 catalyzes the conversion of desmosterol into cholesterol. Disruption of cholesterol homeostasis in neurons may increase cell susceptibility to toxic agents. Because the hippocampus and the subventricular zone, which are affected in AD, are the unique regions containing stem cells with neurogenic potential in the adult brain, it might be hypothesized that this multipotent cell compartment is the predominant source of seladin-1 in normal brain. In the present study, we isolated and characterized human mesenchymal stem cells (hMSC) as a model of cells with the ability to differentiate into neurons. hMSC were then differentiated toward a neuronal phenotype (hMSC-n). These cells were thoroughly characterized and proved to be neurons, as assessed by molecular and electrophysiological evaluation. Seladin-1 expression was determined and found to be significantly reduced in hMSC-n compared to undifferentiated cells. Accordingly, the total content of cholesterol was decreased after differentiation. These original results demonstrate for the first time that seladin-1 is abundantly expressed by stem cells and appear to suggest that reduced expression in AD might be due to an altered pool of multipotent cells.
authors.affiliation: Endocrine Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Benvenuti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Serena
authors.initials: S
authors.lastname: Urbani
authors.forename: Cristiana
authors.initials: C
authors.lastname: Deledda
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rosati
authors.forename: Giovanna
authors.initials: G
authors.lastname: Danza
authors.forename: Stefania
authors.initials: S
authors.lastname: Gelmini
authors.forename: Isabell
authors.initials: I
authors.lastname: Greeve
authors.forename: Matteo
authors.initials: M
authors.lastname: Rossi
authors.forename: Roberto
authors.initials: R
authors.lastname: Maggi
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D015415:Biomarkers; D002118:Calcium / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004594:Electrophysiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008623:Mercaptoethanol / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000502:physiology
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D008623:Mercaptoethanol; D012964:Sodium; D006861:Hydrogen Peroxide; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human; D002118:Calcium