Granulocyte-macrophage colony-stimulating factor and erythropoietin act competitively to induce two different programs of differentiation in the human pluripotent cell line UT-7

O. Hermine, P. Mayeux, M. Titeux, M. T. Mitjavila, N. Casadevall, J. Guichard, N. Komatsu, T. Suda, Y. Miura, W. Vainchenker, J. Breton-Gorius

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53 Citations (Scopus)

Abstract

The UT-7 cell line was established from a patient with a megakaryoblastic leukemia (Komatsu et al, Cancer Res 51:341, 1991). Its proliferation is strictly dependent on the presence of hematopoietic growth factors including erythropoietin (Epo), granulocyte-macrophage colony-stimulating factor (GM- CSF), and interleukin-3 (IL-3). We investigated the differentiation capacities of this cell line under the action of several growth factors, using immunomarkers, flow cytometry, and ultrastructural techniques. In the presence of GM-CSF and IL-3, eosinophil and basophil promyelocytes were detected, as well as a few cells with erythroid and megakaryocytic (MK) differentiation features. In contrast, Epo induced a marked erythroid differentiation with an increase of glycophorin A expression, accompanied by a few hemoglobinized cells. Differentiation induced by the growth factors took 24 to 48 hours to begin, and increased with cell passages to a plateau at 2 weeks of culture. However, this was not only due to a cell selection because the differential effects of Epo and GM-CSF were observed from a single cell clone and the phenotype could be reversed by opposite growth factors, even after a long period of culture. We subsequently investigated the phenotype of UT-7 in the presence of combinations of Epo, IL-3, and GM- CSF, and showed that GM-CSF and IL-3 act predominantly over Epo. This effect was mediated by a rapid downmodulation of Epo receptors by GM-CSF at messenger RNA and binding sites levels, without a change in receptor affinities. On the other hand, Epo had no effect on number and affinity of GM-CSF receptors. This study shows that UT-7 is a growth factor-dependent pluripotent cell line in which commitment may be directed by a hierarchical action of growth factors through an early and rapid transmodulation of growth factor receptors.

Original languageEnglish
Pages (from-to)3060-3069
Number of pages10
JournalBlood
Volume80
Issue number12
DOIs
Publication statusPublished - 1992 Jan 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Hermine, O., Mayeux, P., Titeux, M., Mitjavila, M. T., Casadevall, N., Guichard, J., Komatsu, N., Suda, T., Miura, Y., Vainchenker, W., & Breton-Gorius, J. (1992). Granulocyte-macrophage colony-stimulating factor and erythropoietin act competitively to induce two different programs of differentiation in the human pluripotent cell line UT-7. Blood, 80(12), 3060-3069. https://doi.org/10.1182/blood.v80.12.3060.3060