English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  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.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7B9C-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7B9D-7
Genre: Journal Article
Alternative Title : J.Biol. Chem.

Files

show Files

Locators

show

Creators

show
hide
 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              

Content

show
hide
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.

Details

show
hide
Language(s): eng - English
 Dates: 2010-03-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The Journal of Biological Chemistry
  Alternative Title : J.Biol. Chem.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 285 (19) Sequence Number: - Start / End Page: 14438 - 14449 Identifier: ISSN: 0021-9258