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

Olivier Hermine, Patrick Mayeux, Monique Titeux, Maria Teresa Mitjavila, Nicole Casadevall, Josette Guichard, Norio Komatsu, Toshio Suda, Yasusada Miura, William Vainchenker, Janine Breton-Gorius

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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
Publication statusPublished - 1992 Dec 15

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Granulocyte-Macrophage Colony-Stimulating Factor
Erythropoietin
Intercellular Signaling Peptides and Proteins
Interleukin-3
Cells
Cell Line
Clone cells
Granulocyte-Macrophage Colony-Stimulating Factor Receptors
Growth Differentiation Factors
Erythropoietin Receptors
Glycophorin
Phenotype
Granulocyte Precursor Cells
Erythroid Cells
Growth Factor Receptors
Basophils
Flow cytometry
Eosinophils
Flow Cytometry
Leukemia

ASJC Scopus subject areas

  • Hematology

Cite this

Hermine, O., Mayeux, P., Titeux, M., Mitjavila, M. T., Casadevall, N., Guichard, J., ... 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.

Granulocyte-macrophage colony-stimulating factor and erythropoietin act competitively to induce two different programs of differentiation in the human pluripotent cell line UT-7. / Hermine, Olivier; Mayeux, Patrick; Titeux, Monique; Mitjavila, Maria Teresa; Casadevall, Nicole; Guichard, Josette; Komatsu, Norio; Suda, Toshio; Miura, Yasusada; Vainchenker, William; Breton-Gorius, Janine.

In: Blood, Vol. 80, No. 12, 15.12.1992, p. 3060-3069.

Research output: Contribution to journalArticle

Hermine, O, Mayeux, P, Titeux, M, Mitjavila, MT, 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, vol. 80, no. 12, pp. 3060-3069.
Hermine, Olivier ; Mayeux, Patrick ; Titeux, Monique ; Mitjavila, Maria Teresa ; Casadevall, Nicole ; Guichard, Josette ; Komatsu, Norio ; Suda, Toshio ; Miura, Yasusada ; Vainchenker, William ; Breton-Gorius, Janine. / Granulocyte-macrophage colony-stimulating factor and erythropoietin act competitively to induce two different programs of differentiation in the human pluripotent cell line UT-7. In: Blood. 1992 ; Vol. 80, No. 12. pp. 3060-3069.
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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.",
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AU - Titeux, Monique

AU - Mitjavila, Maria Teresa

AU - Casadevall, Nicole

AU - Guichard, Josette

AU - Komatsu, Norio

AU - Suda, Toshio

AU - Miura, Yasusada

AU - Vainchenker, William

AU - Breton-Gorius, Janine

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