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.

译文

UT-7是一种人类巨核细胞白血病细胞系,其生长和存活绝对依赖于interleukin-3,粒细胞-巨噬细胞集落刺激因子 (gm-csf) 或促红细胞生成素 (EPO)。在用gm-csf长期培养UT-7后,我们分离了一个新的子系UT-7/GM。在EPO处理的UT-7/GM细胞中,血红蛋白浓度以及 γ-珠蛋白和EPO受体mRNA水平显着高于未处理的细胞。相比之下,血小板生成素 (TPO) 处理的UT-7/GM细胞中的血小板因子4和糖蛋白IIb mRNA水平远高于未处理的细胞。某些经TPO处理的细胞具有形态成熟的巨核细胞特征,例如细胞质和多小叶核中的分界膜发达。这些发现表明,UT-7/GM是一种双能细胞系,可以分别通过EPO和TPO诱导分化为红系和巨核细胞系。此外,少数UT-7/GM细胞通过用TPO处理获得高血红蛋白浓度,表明TPO部分诱导了UT-7/GM细胞的红系分化。有趣的是,gm-csf抑制EPO或TPO诱导的红细胞分化和TPO诱导的UT-7/GM细胞的巨核细胞分化。这些结果支持以下假设: 细胞因子会影响谱系承诺或分化所需的基因表达编程。

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