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

被引:29
作者
Clarke, D
Vegiopoulos, A
Crawford, A
Mucenski, M
Bonifer, C
Frampton, J [1 ]
机构
[1] John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DS, England
[2] Univ Leeds, St James Hosp, Mol Med Unit, Leeds LS9 7TF, W Yorkshire, England
[3] Childrens Hosp, Div Pulm Biol, Cincinnati, OH 45229 USA
基金
英国惠康基金;
关键词
c-Myb; knockout; ES cell differentiation; haemopoietic progenitors;
D O I
10.1038/sj.onc.1203661
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3343 / 3351
页数:9
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