In vitro differentiation of c-myb-/- ES cells reveals that the colony forming capacity of unilineage macrophage precursors and myeloid progenitor commitment are c-Myb independent
In vitro differentiation of c-myb-/- ES cells reveals that the colony forming capacity of unilineage macrophage precursors and myeloid progenitor commitment are c-Myb independent
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DOI：
10.1038/sj.onc.1203661
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发表时间：
2000-07-13
期刊：
影响因子：
8
通讯作者：
Frampton, J
中科院分区：
文献类型：
--
作者：
Clarke, D;Vegiopoulos, A;Frampton, J
失活的c-myb等位基因纯合小鼠表现出胚胎（原始）血液形成，但由于未能产生成人（永久）造血而在妊娠第15天左右死亡。最近，它已被证明，在体内确实发生了确定的造血承诺，但在随后的发展方向分化谱系的一些点是妥协。在这里，我们问是否有可能证明这种相同的区别之间的原始和永久性造血的发展过程中，在体内分化的c-myb空ES细胞，这是否可以用来更精确地定义在哪个发展阶段的c-Myb的情况下，块成人造血谱系。我们研究了祖细胞形成的动力学和分化的承诺，使用集落形成试验和RNA和表面抗原表达分析的组合。原始的单系巨噬细胞和红系前体定型可以在没有c-Myb的情况下发展。没有检测到永久性造血特征的前体;然而，我们可以显示转录和表面抗原的表达，这与在早期多潜能阶段阻断的永久性祖细胞的出现一致。
Mice homozygous for an inactivated c-myb allele exhibit embryonic (primitive) blood formation but die at about day 15 of gestation because of a failure to generate adult (definitive) haemopoiesis. Recently, it has been shown that commitment to definitive haemopoiesis does occur in vivo, but that some point in the subsequent development towards the differentiated lineages is compromised. Here we have asked whether it is possible to demonstrate this same distinction between the development of primitive and definitive haemopoiesis during the in vivo differentiation of c-myb null ES cells, and whether this can be used to define more precisely at which developmental stage the absence of c-Myb blocks the adult haemopoietic lineages. We investigated the kinetics of progenitor formation and commitment to differentiation using a combination of colony forming assays and analysis of RNA and surface antigen expression. Primitive unilineage macrophage and erythroid precursor commitment could develop in the absence of c-Myb. No precursors characteristic of definitive haemopoiesis were detected; nevertheless, we could show the expression of programme of transcription and surface antigens which is consistent with the appearance of definitive progenitors blocked at an early multipotential stage.