Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development
Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development
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DOI：
10.1182/blood-2005-09-3846
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发表时间：
2006-08-01
期刊：
影响因子：
20.3
通讯作者：
Ogawa, Minetaro
中科院分区：
文献类型：
--
作者：
Sakamoto, Hiroshi;Dai, Guoyou;Ogawa, Minetaro
已提出确定的造血细胞谱系起源于小鼠胚胎发生过程中的造血内皮细胞。 c-Myb 是一种转录因子，对于最终造血的发育至关重要。为了研究c-Myb在内皮细胞的造血细胞发育中的功能作用，我们将在四环素调节启动子控制下表达的c-myb转基因引入c-myb(-/-)胚胎干(ES)细胞系，目的是诱导c-Myb在任何阶段和任何水平表达。重新接种c-myb(-/-)内皮细胞后诱导c-Myb表达可挽救定形造血祖细胞的产生和增殖，这表明发育中内皮细胞中的c-Myb表达并不是其造血潜力的先决条件。然而，c-Myb 的过度表达阻止了红细胞和巨核细胞的终末分化，并完全阻止了 B 淋巴细胞的发育。我们的结果表明，c-Myb 是控制源自造血内皮细胞的造血祖细胞的分化和增殖的主要因子，并且在每个造血细胞谱系的不同分化步骤中严格定义适当的 c-Myb 蛋白水平。
The definitive hernatopoietic cell lineages have been proposed to originate from hemogenic endothelial cells during mouse embryogenesis. c-Myb is a transcription factor that is essential for the development of definitive hematopoiesis. To investigate the functional role of c-Myb in hernatopoietic cell development from endothelial cells, we introduced a c-myb transgene expressed under the control of a tetracycline-regulated promoter into the c-myb(-/-) embryonic stem (ES) cell line, with the aim of inducing c-Myb expression at any stage and at any level. Induction of c-Myb expression after replating c-myb(-/-) endothelial cells rescued the generation and proliferation of definitive hernatopoietic progenitor cells, suggesting that c-Myb expression in developing endothelial cells is not a prerequisite for their hematogenic potential. Overexpression of c-Myb, however, prevented the terminal differentiation of erythrocytes and megakaryocytes and completely abolished B-lymphocyte development. Our results indicate that c-Myb is a major factor that controls differentiation as well as proliferation of hematopoletic progenitor cells derived from hemogenic endothelial cells, and that appropriate levels of c-Myb protein are strictly defined at distinct differentiation steps of each hernatopoletic cell lineage.