Li C-Y, Zhan Y-Q, Li W, Xu C-W, Xu W-X, Yu D-H, Peng R-Y, Cui Y-F, Yang X, Hou N, Li Y-H, Dong B, Sun H-B, Yang X-M
Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing, China.
Leukemia. 2007 Nov;21(11):2277-86. doi: 10.1038/sj.leu.2404901. Epub 2007 Aug 9.
Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin- bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.
红细胞分化相关基因（EDAG）是一种造血组织特异性基因，在最早的CD34+lin-骨髓（BM）细胞中高表达，并参与造血细胞的增殖和分化。为了研究EDAG在造血过程中的作用，我们建立了由人CD11a启动子驱动的EDAG转基因小鼠模型。转基因小鼠死亡率增加，伴有中性粒细胞严重浸润器官，造血稳态被打破。骨髓中髓系细胞扩增，骨髓生成增强，外周粒细胞增多，脾脏出现髓外造血。与髓系细胞相反，淋巴系分化严重受损，骨髓中B淋巴细胞生成在从前B/前B I向pre-B II阶段转变时受阻，T淋巴细胞发育在最不成熟阶段（DN I）受阻。此外，我们发现EDAG是一种转录调节因子，具有反式激活活性，并在转基因造血干细胞中调节几种关键转录因子如PU.1和Pax5的表达。这些数据表明，EDAG是维持造血谱系分化稳态的关键转录调节因子。
