PUBLICATION
TAZ, a transcriptional modulator of mesenchymal stem cell differentiation
- Authors
- Hong, J.H., Hwang, E.S., McManus, M.T., Amsterdam, A., Tian, Y., Kalmukova, R., Mueller, E., Benjamin, T., Spiegelman, B.M., Sharp, P.A., Hopkins, N., and Yaffe, M.B.
- ID
- ZDB-PUB-050818-12
- Date
- 2005
- Source
- Science (New York, N.Y.) 309(5737): 1074-1078 (Journal)
- Registered Authors
- Amsterdam, Adam, Hopkins, Nancy
- Keywords
- none
- MeSH Terms
-
- Mesenchymal Stem Cells/cytology*
- Mesenchymal Stem Cells/physiology
- Animals
- Protein Structure, Tertiary
- Mice
- Promoter Regions, Genetic
- Gene Expression Regulation, Developmental
- Cell Line
- Adipocytes/cytology*
- Proteins/chemistry
- Proteins/genetics
- Proteins/physiology*
- Transcriptional Activation
- Oligonucleotides, Antisense
- Osteogenesis
- Neoplasm Proteins/metabolism
- Bone Morphogenetic Proteins/pharmacology
- Transcription Factors/chemistry
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Transcription Factors/physiology*
- Transfection
- Zebrafish
- Transforming Growth Factor beta/pharmacology
- Cell Differentiation
- Humans
- Osteoblasts/cytology*
- PPAR gamma/metabolism
- Core Binding Factor Alpha 1 Subunit
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology
- RNA, Small Interfering
- Osteocalcin/genetics
- Bone Morphogenetic Protein 2
- PubMed
- 16099986 Full text @ Science
Citation
Hong, J.H., Hwang, E.S., McManus, M.T., Amsterdam, A., Tian, Y., Kalmukova, R., Mueller, E., Benjamin, T., Spiegelman, B.M., Sharp, P.A., Hopkins, N., and Yaffe, M.B. (2005) TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science (New York, N.Y.). 309(5737):1074-1078.
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 gamma (PPARgamma), 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 PPARgamma-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping