Gangliosides as a potential new class of stem cell markers: the case of GD1a in human bone marrow mesenchymal stem cells.
Owing to their exposure on the cell surface and the possibility of being directly recognized with specific antibodies, glycosphingolipids have aroused great interest in the field of stem cell biology. In the search for specific markers of the differentiation of human bone marrow mesenchymal stem cells (hBMSCs) toward osteoblasts, we studied their glycosphingolipid pattern, with particular attention to gangliosides. After lipid extraction and fractionation, gangliosides, metabolically (3)H-labeled in the sphingosine moiety, were separated by high-performance TLC and chemically characterized by MALDI MS. Upon induction of osteogenic differentiation, a 3-fold increase of ganglioside GD1a was observed. Therefore, the hypothesis of GD1a involvement in hBMSCs commitment toward the osteogenic phenotype was tested by comparison of the osteogenic propensity of GD1a-highly expressing versus GD1a-low expressing hBMSCs and direct addition of GD1a in the differentiation medium. It was found that either the high expression of GD1a in hBMSCs or the addition of GD1a in the differentiation medium favored osteogenesis, providing a remarkable increase of alkaline phosphatase. It was also observed that ganglioside GD2, although detectable in hBMSCs by immunohistochemistry with an anti-GD2 antibody, could not be recognized by chemical analysis, likely reflecting a case, not uncommon, of molecular mimicry.
Departments of Biomedical Sciences for Health, and University of Milan, Segrate (Milan), Italy.
Sonia
S
Bergante
Enrica
E
Torretta
Pasquale
P
Creo
Nadia
N
Sessarego
Nadia
N
Papini
Marco
M
Piccoli
Chiara
C
Fania
Federica
F
Cirillo
Erika
E
Conforti
Andrea
A
Ghiroldi
Cristina
C
Tringali
Bruno
B
Venerando
Adalberto
A
Ibatici
Cecilia
C
Gelfi
Guido
G
Tettamanti
Luigi
L
Anastasia
D000469:Alkaline Phosphatase / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D020405:Dermis / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053495:Osteopontin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013107:Sphingolipids / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D005732:Gangliosides; D013107:Sphingolipids; D053495:Osteopontin; C021298:ganglioside, GD1a; D000469:Alkaline Phosphatase
osteogenic differentiation; sphingolipids; stem cells characterization