In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM.
UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.
Komatsu
N
N
Department of Medicine, Jichi Medical School, Minamikawachi-machi, Tochigi-ken, Japan.
Kirito
K
K
Shimizu
R
R
Kunitama
M
M
Yamada
M
M
Uchida
M
M
Takatoku
M
M
Eguchi
M
M
Miura
Y
Y
D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D004912:Erythrocytes / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology*; D013926:Thrombopoietin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin