Microarray analyses of transdifferentiated mesenchymal stem cells.
The molecular events associated with the age-related gain of fatty tissue in human bone marrow are still largely unknown. Besides enhanced adipogenic differentiation of mesenchymal stem cells (MSCs), transdifferentiation of osteoblast progenitors may contribute to bone-related diseases like osteopenia. Transdifferentiation of MSC-derived osteoblast progenitors into adipocytes and vice versa has previously been proven feasible in our cell culture system. Here, we focus on mRNA species that are regulated during transdifferentiation and represent possible control factors for the initiation of transdifferentiation. Microarray analyses comparing transdifferentiated cells with normally differentiated cells exhibited large numbers of reproducibly regulated genes for both, adipogenic and osteogenic transdifferentiation. To evaluate the relevance of individual genes, we designed a scoring scheme to rank genes according to reproducibility, regulation level, and reciprocity between the different transdifferentiation directions. Thereby, members of several signaling pathways like FGF, IGF, and Wnt signaling showed explicitly differential expression patterns. Additional bioinformatic analysis of microarray analyses allowed us to identify potential key factors associated with transdifferentiation of adipocytes and osteoblasts, respectively. Fibroblast growth factor 1 (FGF1) was scored as one of several lead candidate gene products to modulate the transdifferentiation process and is shown here to exert inhibitory effects on adipogenic commitment and differentiation.
Schilling
Tatjana
T
University of Würzburg, Orthopedic Department, Orthopedic Center for Musculoskeletal Research, Würzburg, Germany.
Küffner
Robert
R
Klein-Hitpass
Ludger
L
Zimmer
Ralf
R
Jakob
Franz
F
Schütze
Norbert
N
D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology; D054338:Cell Transdifferentiation / Q000235:genetics*; D002478:Cells, Cultured / Q000378:metabolism; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction
D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1