TAZ, a transcriptional modulator of mesenchymal stem cell differentiation.
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.
Hong
Jeong-Ho
JH
Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.
Hwang
Eun Sook
ES
McManus
Michael T
MT
Amsterdam
Adam
A
Tian
Yu
Y
Kalmukova
Ralitsa
R
Mueller
Elisabetta
E
Benjamin
Thomas
T
Spiegelman
Bruce M
BM
Sharp
Phillip A
PA
Hopkins
Nancy
N
Yaffe
Michael B
MB
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
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