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Blood, 15 July 2008, Vol. 112, No. 2, pp. 295-307.
Prepublished online as a Blood First Edition Paper on March 10, 2008; DOI 10.1182/blood-2007-07-103697.
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Submitted July 26, 2007
Accepted March 3, 2008
PDGF, TGF-b and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSC into adipogenic, chondrogenic and ostoegenic lineages
Felicia Ng, Shayne Boucher, Susie Koh, Konduru SR Sastry, Lucas Chase, Uma Lakshmipathy, Cleo Choong, Zheng Yang, Mohan C Vemuri, Mahendra S Rao, and Vivek Tanavde*
Genome and Gene Expression Analaysis Group, Bioinformatics Institute, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
Stem Cells and Regenerative Medicine, Invitrogen Corporation, Carlsbad, CA, United States
Laboratory of Stem Cell Biology, Singapore Stem Cell Consortium, Singapore, Singapore
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore Tissue Engineering Program, National University of Singapore, Singapore, Singapore
* Corresponding author; email: vivek{at}bii.a-star.edu.sg.
We compared the transcriptomes of marrow derived MSCs with differentiated adipocytes, osteocytes and chondrocytes derived from these MSCs. Using global gene expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic and osteogenic lineages. We identified Activin mediated TGF- signaling, PDGF signaling and FGF signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function.
Since growth and differentiation are tightly linked processes, we also examined the importance of these three pathways in MSC growth. These three pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth whereas a combination of TGF- , PDGF and -FGF was sufficient to grow MSCs in a serum free medium up to 5 passages. Thus this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.

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