Retraction: Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease
| Autor: | Orlando Domínguez, Antonio Herrera-Merchan, Susana González, José M. Ligos, A de Molina, Lorena Arranz |
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| Rok vydání: | 2017 |
| Předmět: |
Time Factors
Cell Transplantation General Physics and Astronomy Mice Transgenic Cell Separation Biology Models Biological General Biochemistry Genetics and Molecular Biology Histones Mice Gene duplication Animals Enhancer of Zeste Homolog 2 Protein Transgenes Cell Proliferation Regulation of gene expression Multidisciplinary Myeloproliferative Disorders Models Genetic Gene Expression Profiling EZH2 Polycomb Repressive Complex 2 Granulocyte-Macrophage Colony-Stimulating Factor General Chemistry Flow Cytometry Hematopoietic Stem Cells Retraction DNA-Binding Proteins Haematopoiesis Gene Expression Regulation Histone methyltransferase Immune System Cancer research Ectopic expression Stem cell Retracted Publication Transcription Factors |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Recent evidence shows increased and decreased expression of Ezh2 in cancer, suggesting a dual role as an oncogene or tumour suppressor. To investigate the mechanism by which Ezh2-mediated H3K27 methylation leads to cancer, we generated conditional Ezh2 knock-in (Ezh2-KI) mice. Here we show that induced Ezh2 haematopoietic expression increases the number and proliferation of repopulating haematopoietic stem cells. Ezh2-KI mice develop myeloproliferative disorder, featuring excessive myeloid expansion in bone marrow and spleen, leukocytosis and splenomegaly. Competitive and serial transplantations demonstrate progressive myeloid commitment of Ezh2-KI haematopoietic stem cells. Transplanted self-renewing haematopoietic stem cells from Ezh2-KI mice induce myeloproliferative disorder, suggesting that the Ezh2 gain-of-function arises in the haematopoietic stem cell pool, and not at later stages of myelopoiesis. At the molecular level, Ezh2 regulates haematopoietic stem cell-specific genes such as Evi-1 and Ntrk3, aberrantly found in haematologic malignancies. These results demonstrate a stem cell-specific Ezh2 oncogenic role in myeloid disorders, and suggest possible therapeutic applications in Ezh2-related haematological malignancies. |
| Databáze: | OpenAIRE |
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