English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone

Tolkachov, A., Fischer, C., Ambrosi, T. H., Bothe, A. M., Han, C.-T., Muenzner, M., et al. (2018). Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone. Molecular and Cellular Biology (Washington, DC), 38(12): e00599-17. doi:10.1128/MCB.00599-17.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0003-517C-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-517D-6
Genre: Journal Article

Files

show Files
hide Files
:
Tolkachov.pdf (Publisher version), 3MB
Name:
Tolkachov.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2018 American Society for Microbiology
License:
-

Locators

show

Creators

show
hide
 Creators:
Tolkachov, Alexander , Author
Fischer, Cornelius , Author
Ambrosi, Thomas H. , Author
Bothe, Anna Melissa1, Author              
Han, Chung-Ting , Author
Muenzner, Matthias , Author
Mathia, Susanne, Author
Salminen, Marjo, Author
Seifert, Georg , Author
Thiele, Mario , Author
Duda, Georg N. , Author
Meijsing, Sebastiaan1, Author              
Sauer, Sascha, Author
Schulz, Tim J. , Author
Schupp, Michael , Author
Affiliations:
1Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479641              

Content

show
hide
Free keywords: GATA2; bone; cell differentiation; mesenchymal stem cell; osteoblast; trabecularization
 Abstract: The transcription factor GATA2 is required for expansion and differentiation of hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs), GATA2 blocks adipogenesis, but its biological relevance and underlying genomic events are unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs binds near genes involved in skeletal system development and colocalizes with motifs for FOX and HOX transcription factors, known regulators of skeletal development. Ectopic GATA2 blocks osteoblastogenesis by interfering with SMAD1/5/8 activation. MSC-specific deletion of GATA2 in mice increases the numbers and differentiation capacity of bone-derived precursors, resulting in elevated bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs the trabecularization and mechanical strength of bone, involving reduced MSC expression of the osteoclast inhibitor osteoprotegerin and increased osteoclast numbers. Thus, GATA2 affects bone turnover via MSC-autonomous and indirect effects. By regulating bone trabecularization, GATA2 expression in the osteogenic lineage may contribute to the anatomical and cellular microenvironment of the HSC niche required for hematopoiesis.

Details

show
hide
Language(s): eng - English
 Dates: 2018-03-092018-05-292018-06-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1128/MCB.00599-17
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Molecular and Cellular Biology (Washington, DC)
  Other : Mol Cell Biol
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: American Society for Microbiology (ASM)
Pages: - Volume / Issue: 38 (12) Sequence Number: e00599-17 Start / End Page: - Identifier: ISSN: 0270-7306
CoNE: https://pure.mpg.de/cone/journals/resource/954925502188