Gene expression profiles of human mesenchymal stem cells stimulated with canonical Wnt signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16186 | GEO | 2009/06/14
SECONDARY ACCESSION(S): PRJNA115077
REPOSITORIES: GEO
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Project description:Foxp3 is crucial for both the development and function of regulatory T cells (Treg),however the post-translational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that TCF1 and Foxp3 interact in the nucleus of Treg, and that active Wnt-signaling disrupts Foxp3 transcriptional activity. Utilizing a global ChIP-seq comparison we demonstrate considerable overlap between Foxp3 and Wnt target genes in Treg. Activation of Wnt signaling significantly reduces Treg-mediated suppression both in vitro and in vivo, while disruption of Wnt signaling in Treg enhances their suppressive capacity. Activation of effector T cells increases Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced by activated mononuclear cells under inflammatory conditions represses Treg function allowing a productive immune response, but if uncontrolled could lead to the development of autoimmunity. Beta catenin ChIP-seq in Treg
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Project description:Considerable information has accumulated about components of bone marrow that regulate survival, self-renewal and differentiation of hematopoietic cells. We have now studied Wnt signaling in that context, assessing influences on human and murine hematopoiesis. Microarray, PCR and staining experiments revealed that OP9 acquired osteoblastic characteristics while down-regulating some features associated with mesenchymal stem cells. This included down-regulation of Angiopoietin 1, c-Kit ligand and VCAM-1 expression. In contrast, production of decorin, tenascins and fibromodulin markedly increased. At least one of these extracellular matrix components, decorin is a regulator of hematopoiesis. That is, addition of the protein to OP9 co-cultures causes changes similar to Wnt3a. Two control samples (LZR1 & LZR2) were analyzed from OP9 mouse stromal cells transfected with vector only, and two experimental samples (W3A1 & W3A2) were analyzed from OP9 cells transfected with vector containing the Wnt3A gene.
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