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  • Original Paper
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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

Oncogene volume 19, pages 3343–3351 (2000)Cite this article

Abstract

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.

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Acknowledgements

We thank all members of the Frampton and Bonifer labs for discussions and advice. This work was funded by the Wellcome Trust, the Candlelighter's Trust and the Leukaemia Research Fund. J Frampton is a Wellcome Trust Senior Research Fellow.

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Authors and Affiliations

  1. University of Leeds, St. James's University Hospital, Molecular Medicine Unit, Leeds, LS9 7TF, UK

    Deborah Clarke, Alexandros Vegiopoulos & Constanze Bonifer

  2. Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK

    Anthony Crawford & Jonathan Frampton

  3. Division of Pulmonary Biology, Children's Hospital, Cincinnati, Ohio, USA

    Michael Mucenski

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  1. Deborah Clarke
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Clarke, D., Vegiopoulos, A., Crawford, A. et al. 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. Oncogene 19, 3343–3351 (2000). https://doi.org/10.1038/sj.onc.1203661

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