Development of hematopoietic populations through the process of differentiation is critical for proper hematopoiesis. The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is a master regulator of myeloid differentiation, and the identification of C/EBPα target genes is key to understand this process. Here we identified the Ecotropic Viral Integration Site 2B (EVI2B) gene as a direct target of C/EBPα. We showed that the product of the gene, the transmembrane glycoprotein EVI2B (CD361), is abundantly expressed on the surface of primary hematopoietic cells, the highest levels of expression being reached in mature granulocytes. Using shRNA-mediated downregulation of EVI2B in human and murine cell lines and in primary hematopoietic stem and progenitor cells, we demonstrated impaired myeloid lineage development and altered progenitor functions in EVI2B-silenced cells. We showed that the compromised progenitor functionality in Evi2b-depleted cells can be in part explained by deregulation of cell proliferation and apoptosis. In addition, we generated an Evi2b knockout murine model and demonstrated altered properties of hematopoietic progenitors, as well as impaired G-CSF dependent myeloid colony formation in the knockout cells. Remarkably, we found that EVI2B is significantly downregulated in human acute myeloid leukemia samples characterized by defects in CEBPA. Altogether, our data demonstrate that EVI2B is a downstream target of C/EBPα, which regulates myeloid differentiation and functionality of hematopoietic progenitors.

• MeSH
• akutní myeloidní leukemie metabolismus   patologie   MeSH
• apoptóza MeSH
• buněčná diferenciace účinky léků   MeSH
• buňky kostní dřeně cytologie   MeSH
• down regulace účinky léků   MeSH
• estradiol farmakologie   MeSH
• faktor stimulující kolonie granulocytů farmakologie   MeSH
• granulocyty cytologie   metabolismus   MeSH
• hematopoetické kmenové buňky cytologie   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• membránové glykoproteiny antagonisté a inhibitory   genetika   metabolismus   MeSH
• membránové proteiny antagonisté a inhibitory   genetika   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• proliferace buněk účinky léků   MeSH
• promotorové oblasti (genetika) MeSH
• protein alfa vázající zesilovač transkripce CCAAT genetika   metabolismus   MeSH
• RNA interference MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH