Genome-wide screening by cDNA microarray of genes associated with matrix mineralization by human mesenchymal stem cells in vitro.
Using a culture system that facilitates osteogenic differentiation of bone marrow-derived human mesenchymal stem cells, we analyzed gene-expression profiles during the mineralization process by means of a cDNA microarray system consisting of 23,040 genes. We compared expression profiles of the cells at days 3, 15, and 27 of incubation in media containing either a combination of 0.1 microM dexamethasone, 0.05 mM ascorbic acid-2-phosphate, and 10 mM beta-glycerophosphate, dexamethasone only, ascorbic acid-2-phosphate plus beta-glycerophosphate, or medium without any of these osteogenic supplements. Histochemical analysis revealed osteogenic differentiation of cells incubated in the presence of all three agents, but not in the other cultures. Comparison of the expression profiles disclosed transcriptional stimulation of 55 genes and repression of 82 genes among more than 20,000 examined. A set of differentially expressed genes we report here should contribute to a better understanding of the process of mineralization in the matrix surrounding human mesenchymal stem cells.
Doi
Mitsuhito
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nagano
Akira
A
Nakamura
Yusuke
Y
D000970:Antineoplastic Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D008648:Mesoderm / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D018076:DNA, Complementary; D005994:Glycerophosphates; C011669:ascorbate-2-phosphate; D003907:Dexamethasone; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid