TAZ, a transcriptional modulator of mesenchymal stem cell differentiation

Jeong-Ho Hong, Eun Sook Hwang, Michael T. McManus, Adam Amsterdam, Yu Tian, Ralitsa Kalmukova, Elisabetta Mueller, Thomas Benjamin, Bruce M. Spiegelman, Phillip A. Sharp, Nancy Hopkins, Michael B. Yaffe

Research output: Contribution to journalArticle

640 Citations (Scopus)

Abstract

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 γ (PPARγ), 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 PPARγ-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.

Original languageEnglish
Pages (from-to)1074-1078
Number of pages5
JournalScience
Volume309
Issue number5737
DOIs
Publication statusPublished - 2005 Aug 12
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Cell Differentiation
Peroxisome Proliferator-Activated Receptors
Transcription Factors
14-3-3 Proteins
Zebrafish
Osteoblasts
Adipocytes
Genes
Carrier Proteins
Cell Culture Techniques
Fibroblasts
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Hong, J-H., Hwang, E. S., McManus, M. T., Amsterdam, A., Tian, Y., Kalmukova, R., ... Yaffe, M. B. (2005). TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science, 309(5737), 1074-1078. https://doi.org/10.1126/science.1110955

TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. / Hong, Jeong-Ho; Hwang, Eun Sook; McManus, Michael T.; Amsterdam, Adam; Tian, Yu; Kalmukova, Ralitsa; Mueller, Elisabetta; Benjamin, Thomas; Spiegelman, Bruce M.; Sharp, Phillip A.; Hopkins, Nancy; Yaffe, Michael B.

In: Science, Vol. 309, No. 5737, 12.08.2005, p. 1074-1078.

Research output: Contribution to journalArticle

Hong, J-H, Hwang, ES, McManus, MT, Amsterdam, A, Tian, Y, Kalmukova, R, Mueller, E, Benjamin, T, Spiegelman, BM, Sharp, PA, Hopkins, N & Yaffe, MB 2005, 'TAZ, a transcriptional modulator of mesenchymal stem cell differentiation', Science, vol. 309, no. 5737, pp. 1074-1078. https://doi.org/10.1126/science.1110955
Hong J-H, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005 Aug 12;309(5737):1074-1078. https://doi.org/10.1126/science.1110955
Hong, Jeong-Ho ; Hwang, Eun Sook ; McManus, Michael T. ; Amsterdam, Adam ; Tian, Yu ; Kalmukova, Ralitsa ; Mueller, Elisabetta ; Benjamin, Thomas ; Spiegelman, Bruce M. ; Sharp, Phillip A. ; Hopkins, Nancy ; Yaffe, Michael B. / TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. In: Science. 2005 ; Vol. 309, No. 5737. pp. 1074-1078.
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