Wnt Target Genes Identified by DNA Microarrays in Immature CD34+ Thymocytes Regulate Proliferation and Cell Adhesion
| Autor: | Miranda R. M. Baert, Edwin F. E. de Haas, Frank J. T. Staal, Mascha van Noort, Jacques J.M. van Dongen, Caroline M. M. van den Burg, Floor Weerkamp |
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| Rok vydání: | 2004 |
| Předmět: |
Beta-catenin
Lymphoid Enhancer-Binding Factor 1 Immunology Antigens CD34 Thymus Gland Transfection Wnt3 Protein Mice Genes Reporter T-Lymphocyte Subsets Transduction Genetic Proto-Oncogene Proteins Cell Adhesion T Cell Transcription Factor 1 Animals Humans Immunology and Allergy Hepatocyte Nuclear Factor 1-alpha Child Cell adhesion beta Catenin Oligonucleotide Array Sequence Analysis Cell-Free System biology Cell adhesion molecule Wnt signaling pathway Proteins LRP6 Cell Differentiation LRP5 Zebrafish Proteins Molecular biology Cell biology DNA-Binding Proteins Mice Inbred C57BL Wnt Proteins Cytoskeletal Proteins Thymocyte Retroviridae Protein Biosynthesis Catenin Trans-Activators biology.protein Lithium Chloride Cell Division Signal Transduction Transcription Factors |
| Zdroj: | The Journal of Immunology. 172:1099-1108 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.172.2.1099 |
| Popis: | The thymus is seeded by very small numbers of progenitor cells that undergo massive proliferation before differentiation and rearrangement of TCR genes occurs. Various signals mediate proliferation and differentiation of these cells, including Wnt signals. Wnt signals induce the interaction of the cytoplasmic cofactor β-catenin with nuclear T cell factor (TCF) transcription factors. We identified target genes of the Wnt/β-catenin/TCF pathway in the most immature (CD4−CD8−CD34+) thymocytes using Affymetrix DNA microarrays in combination with three different functional assays for in vitro induction of Wnt signaling. A relatively small number (∼30) of genes changed expression, including several proliferation-inducing transcription factors such as c-fos and c-jun, protein phosphatases, and adhesion molecules, but no genes involved in differentiation to mature T cell stages. The adhesion molecules likely confine the proliferating immature thymocytes to the appropriate anatomical sites in the thymus. For several of these target genes, we validated that they are true Wnt/β-catenin/TCF target genes using real-time quantitative PCR and reporter gene assays. The same core set of genes was repressed in Tcf-1-null mice, explaining the block in early thymocyte development in these mice. In conclusion, Wnt signals mediate proliferation and cell adhesion, but not differentiation of the immature thymic progenitor pool. |
| Databáze: | OpenAIRE |
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