Tamura Akihiro, Hirai Hideyo, Yokota Asumi, Kamio Naoka, Sato Atsushi, Shoji Tsukimi, Kashiwagi Takahiro, Torikoshi Yusuke, Miura Yasuo, Tenen Daniel G, Maekawa Taira
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
Cancer Science Institute, National University of Singapore, Singapore; and.
Blood. 2017 Oct 19;130(16):1809-1818. doi: 10.1182/blood-2017-03-772962. Epub 2017 Aug 14.
The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis are largely unknown. Here, we investigated the roles of C/EBPβ in monopoiesis. Further subdivision of monocytes revealed that messenger RNA was highly upregulated in Ly6C monocytes in bone marrow. Accordingly, the number of Ly6C monocytes was significantly reduced in mice. Bone marrow chimera experiments and -Cre-mediated deletion of revealed a cell-intrinsic and monocyte-specific requirement for C/EBPβ in monopoiesis. In mice, turnover of Ly6C monocytes was highly accelerated and apoptosis of Ly6C monocytes was increased. Expression of , which encodes a receptor for macrophage colony-stimulating factor, was significantly reduced in Ly6C monocytes of mice. C/EBPβ bound to positive regulatory elements of and promoted its transcription. Collectively, these results indicate that C/EBPβ is a critical factor for Ly6C monocyte survival, at least in part through upregulation of
转录因子CCAAT/增强子结合蛋白β(C/EBPβ)在单核细胞/巨噬细胞中高表达。然而,其在单核细胞生成中的作用尚不清楚。在此,我们研究了C/EBPβ在单核细胞生成中的作用。对单核细胞的进一步细分显示,骨髓中Ly6C单核细胞中的信使核糖核酸高度上调。相应地,小鼠中Ly6C单核细胞的数量显著减少。骨髓嵌合体实验以及-Cre介导的缺失显示,单核细胞生成中C/EBPβ具有细胞内在性和单核细胞特异性需求。在小鼠中,Ly6C单核细胞的更新高度加速,Ly6C单核细胞的凋亡增加。在小鼠的Ly6C单核细胞中,编码巨噬细胞集落刺激因子受体的的表达显著降低。C/EBPβ与的正调控元件结合并促进其转录。总体而言,这些结果表明,C/EBPβ是Ly6C单核细胞存活的关键因素,至少部分是通过上调
(注:原文中存在一些未明确的内容,如“-Cre-mediated deletion of revealed”“Expression of, which encodes a receptor for macrophage colony-stimulating factor”等表述不完整,翻译可能会受一定影响。)