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  Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) regulates differentiation fate of human mesenchymal (stromal) stem cells through canonical Wnt signalling and C/EBP

Qiu, W., Hu, Y., Andersen, T. E., Jafari, A., Li, N., Wei Chen, W. C., et al. (2010). Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) regulates differentiation fate of human mesenchymal (stromal) stem cells through canonical Wnt signalling and C/EBP. The Journal of Biological Chemistry, 285(19), 14438-14449. doi:10.1074/jbc.M109.052001.

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Genre: Journal Article
Alternative Title : J.Biol. Chem.

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 Creators:
Qiu, Weimin, Author
Hu, Yuhui1, Author           
Andersen, Tom E., Author
Jafari, Abbas, Author
Li, Na2, Author           
Wei Chen, Wei Chen3, Author
Kassem, Moustapha, Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Computational Epigenetics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479658              
3Max Planck Society, ou_persistent13              

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Free keywords: C/EBP Transcription Factor; Cell Differentiation; Gene Regulation; Stem Cell; Wnt Pathway; Adipogenesis; Human Mesenchymal Stem Cell; Osteogenesis
 Abstract: Mechanisms controlling human multipotent mesenchymal (stromal) stem cell (hMSC) differentiation into osteoblasts or adipocytes are poorly understood. We have previously demonstrated that Wnt signaling in hMSC enhanced osteoblast differentiation and inhibited adipogenesis by comparing two hMSC cell lines overexpressing mutated forms of the Wnt co-receptor LRP5: T253I (hMSC-LRP5T253) and T244M (hMSC-LRP5T244) conducting high and low level of Wnt signaling, respectively. To explore the underlying molecular mechanisms, we compared gene expression profiles of hMSC-LRP5T253 and hMSC-LRP5T244 treated with Wnt3a using whole genome expression microarrays and found that TNFRSF19 is differentially up-regulated between the two cells lines. Bioinformatic analysis and dual luciferase assay of its promoter revealed that TNFRSF19 transcript 2 (TNFRSF19.2) is a target of canonical Wnt signaling. Knocking down TNFRSF19 in hMSC-LRP5T253 cells decreased Wnt3a-induced osteoblast differentiation marker alkaline phosphate activity and its overexpression in hMSC-LRP5T244 cells increased alkaline phosphate activity. In addition, TNFRSF19 was negatively regulated by adipogenic transcription factor CCAAT/enhancer-binding proteins (C/EBP). Knocking down TNFRSF19 in hMSC-LRP5T253 cells or its overexpression in hMSC-LRP5T244 cells significantly increased or decreased adipogenesis, respectively. In conclusion, we revealed a novel function of TNFRSF19 as a factor mediating differentiation signals that determine the hMSC differentiating fate into osteoblasts or adipocytes.

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Language(s): eng - English
 Dates: 2010-03-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
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Title: The Journal of Biological Chemistry
  Alternative Title : J.Biol. Chem.
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 285 (19) Sequence Number: - Start / End Page: 14438 - 14449 Identifier: ISSN: 0021-9258