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Science 12 August 2005:
Vol. 309. no. 5737, pp. 1074 - 1078
DOI: 10.1126/science.1110955
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Reports

TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation

Jeong-Ho Hong,1 Eun Sook Hwang,3 Michael T. McManus,1 Adam Amsterdam,1 Yu Tian,4 Ralitsa Kalmukova,1 Elisabetta Mueller,5 Thomas Benjamin,4 Bruce M. Spiegelman,5 Phillip A. Sharp,1 Nancy Hopkins,1 Michael B. Yaffe1,2*

Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator–activated receptor {gamma} (PPAR{gamma}), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3–binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPAR{gamma}-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.

1 Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.
2 Division of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.
3 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
4 Department of Pathology, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.
5 Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: myaffe{at}mit.edu

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