Neuronal differentiation of human mesenchymal stem cells: changes in the expression of the Alzheimer's disease-related gene seladin-1.
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.
Benvenuti
Susanna
S
Endocrine Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.
Saccardi
Riccardo
R
Luciani
Paola
P
Urbani
Serena
S
Deledda
Cristiana
C
Cellai
Ilaria
I
Francini
Fabio
F
Squecco
Roberta
R
Rosati
Fabiana
F
Danza
Giovanna
G
Gelmini
Stefania
S
Greeve
Isabell
I
Rossi
Matteo
M
Maggi
Roberto
R
Serio
Mario
M
Peri
Alessandro
A
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
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