Miura Y, Kirito K, Komatsu N
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Acta Haematol. 1998;99(3):180-4. doi: 10.1159/000040834.
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. Among its sublines, UT-7/GM, which remains undifferentiated in the presence of GM-CSF, has a bipotency showing differentiation into erythroid or megakaryocytic cell lineages in the presence of EPO or thrombopoietin (TPO), respectively. To investigate the mechanism underlying determination of cell differentiation, we investigated the role of signal transducers and activators of transcription (STAT) in EPO-induced erythroid differentiation. UT-7 cells grow in response to GM-CSF and EPO but do not differentiate into mature cells. UT-7/GM cells grow in response to GM-CSF and differentiate into erythroid cells by EPO. In UT-7 cells, both GM-CSF and EPO induced the activation of Stat1 alpha, Stat3 and Stat5. In UT-7/GM cells, EPO activated Stat5 alone, although the activation of Stat1 alpha, Stat3, and Stat5 was induced by GM-CSF or TPO. In addition, GM-CSF inhibited EPO-induced erythroid differentiation and concomitantly activated Stat1 alpha and Stat3 in UT-7/GM cells even in the presence of EPO. Further we transfected Stat1 alpha, Stat3 cDNA or both into UT-7/GM cells. Hemoglobin-positive cells were decreased in the stable transfectants stimulated with EPO. These results indicate that Stat1 alpha and Stat3 have an inhibitory effect on the EPO-induced erythroid differentiation, and more complicated combination of transcription factors may play an important role in the decision of cell differentiation.
UT-7是一种人巨核母细胞白血病细胞系，其生长和存活绝对依赖于白细胞介素-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）。在其亚系中，UT-7/GM在GM-CSF存在下保持未分化状态，具有双能性，分别在EPO或血小板生成素（TPO）存在下分化为红系或巨核细胞系。为了研究细胞分化决定的潜在机制，我们研究了信号转导和转录激活因子（STAT）在EPO诱导的红系分化中的作用。UT-7细胞在GM-CSF和EPO刺激下生长，但不会分化为成熟细胞。UT-7/GM细胞在GM-CSF刺激下生长，并在EPO作用下分化为红系细胞。在UT-7细胞中，GM-CSF和EPO均诱导Stat1α、Stat3和Stat5的激活。在UT-7/GM细胞中，EPO单独激活Stat5，尽管GM-CSF或TPO可诱导Stat1α、Stat3和Stat5的激活。此外，即使在有EPO存在的情况下，GM-CSF仍可抑制UT-7/GM细胞中EPO诱导的红系分化，并同时激活Stat1α和Stat3。进一步地，我们将Stat1α、Stat3的cDNA或两者转染到UT-7/GM细胞中。在用EPO刺激的稳定转染细胞中，血红蛋白阳性细胞减少。这些结果表明，Stat1α和Stat3对EPO诱导的红系分化具有抑制作用，转录因子更复杂的组合可能在细胞分化的决定中起重要作用。
