Coordination of erythropoiesis by the transcription factor c-Myb
Coordination of erythropoiesis by the transcription factor c-Myb
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DOI：
10.1182/blood-2005-07-2968
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发表时间：
2006-06-15
期刊：
影响因子：
20.3
通讯作者：
Frampton, Jon
中科院分区：
文献类型：
--
作者：
Vegiopoulos, Alexandros;Garcia, Paloma;Frampton, Jon
在白血病细胞模型中已经建立了转录因子c-Myb参与促进红系细胞增殖和抑制红系细胞分化。在c-myb敲除和敲低小鼠中观察到的贫血表型突出了c-Myb在红细胞生成中的关键作用。然而，确定这些小鼠中红细胞生成失败的原因以及c-Myb在红系祖细胞中的精确功能仍然是难以捉摸的。我们研究了在c-Myb蛋白水平降低的条件下红系细胞的发育，并报告了c-Myb在促进红系细胞谱系定型和向成红细胞阶段进展中的意想不到的作用。c-myb敲低的红系集落形成单位（CFU-E）阶段祖细胞显示出不成熟的表型和几种造血调节因子的异常表达。为了扩展我们的研究结果，我们分析了正常富集红系祖细胞对floxed c-myb等位基因诱导破坏的反应。与c-myb敲低表型一致，我们表明c-Myb是红系细胞中c-Kit受体表达的严格要求。
The involvement of the transcription factor c-Myb in promoting the proliferation and inhibition of erythroid cell differentiation has been established in leukemia cell models. The anemia phenotype observed in c-myb knockout and knockdown mice highlights a critical role for c-Myb in erythropoiesis. However, determining the reason for the failure of erythropoiesis in these mice and the precise function of c-Myb in erythroid progenitors remains elusive. We examined erythroid development under conditions of reduced c-Myb protein levels and report an unexpected role for c-Myb in the promotion of commitment to the erythroid lineage and progression to erythroblast stages. c-myb knockdown erythroid colony-forming unit (CFU-E) stage progenitors displayed an immature phenotype and aberrant expression of several hematopoietic regulators. To extend our findings, we analyzed the response of normal enriched erythroid progenitors to inducible disruption of a floxed c-myb allele. In agreement with the c-myb knockdown phenotype, we show that c-Myb is strictly required for expression of the c-Kit receptor in erythroid cells.