title: TAZ, a transcriptional modulator of mesenchymal stem cell differentiation.
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.
authors.affiliation: Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
authors.forename: Michael T
authors.initials: MT
authors.lastname: McManus
authors.forename: Adam
authors.initials: A
authors.lastname: Amsterdam
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Ralitsa
authors.initials: R
authors.lastname: Kalmukova
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Benjamin
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
authors.forename: Nancy
authors.initials: N
authors.lastname: Hopkins
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
mesh_terms: D000217:Acyltransferases; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D047495:PPAR gamma; D011506:Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D015675:Osteocalcin; D000217:Acyltransferases; C486363:tafazzin protein, mouse; C108675:TAFAZZIN protein, human