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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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. / Clarke, D; Vergioupoulos, A; Crawford, A; Mucenski, M; Bonifer, Constanze; Frampton, Jon.
In: Oncogene, Vol. 19, No. 30, 31.07.2013, p. 3343-3351.Research output: Contribution to journal › Article › peer-review
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T1 - 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
AU - Clarke, D
AU - Vergioupoulos, A
AU - Crawford, A
AU - Mucenski, M
AU - Bonifer, Constanze
AU - Frampton, Jon
PY - 2013/7/31
Y1 - 2013/7/31
N2 - 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 vitro 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 a programme of transcription and surface antigens which is consistent with the appearance of definitive progenitors blocked at an early multipotential stage.
AB - 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 vitro 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 a programme of transcription and surface antigens which is consistent with the appearance of definitive progenitors blocked at an early multipotential stage.
KW - in vitro
KW - c-myb(-/-) ES cells
KW - unilineage macrophage
KW - myeloid progenitor commitment
M3 - Article
VL - 19
SP - 3343
EP - 3351
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 30
ER -