The granulocyte colony-stimulating factor receptor supports erythroid differentiation in the absence of the erythropoietin receptor or Stat5

被引:12
作者
Millot, GA [1 ]
Svinarchuk, F [1 ]
Lacout, C [1 ]
Vainchenker, W [1 ]
Dumenil, D [1 ]
机构
[1] Inst Gustave Roussy, Lab Hematopoiese & Cellules Souches, INSERM, U362, F-94805 Villejuif, France
关键词
G-CSF receptor; erythroid differentiation; haematopoiesis; EPO-R knock-out; STATs;
D O I
10.1046/j.1365-2141.2001.02591.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To evaluate the functional conservation of signal transduction mechanisms between haematopoietic receptors and to characterize the molecules activated in this phenomenon, we introduced granulocyte colony-stimulating factor receptor (G-CSFR) cDNA into mouse fetal liver cells using a retroviral vector. In semi-solid medium assays, G-CSFR-infected cells gave rise to all types of colonies [granulocyte-macrophage (GM), megakaryocyte (MK) and mixed lineage (GEMM) colony-forming units (CFU) and erythroid burst-forming units (BFU-E)] in the presence of G-CSF alone. The direct effect of G-CSF on erythroid differentiation of G-CSFR-transduced erythroid progenitors was demonstrated by the development of erythroid colonies using G-CSFR-expressing Lin(-) cells cloned at one cell per well in liquid culture in the presence of G-CSF. Interestingly, while Stat5, but not Stat3, was activated in erythroid cells in response to erythropoietin (EPO), both were activated in erythroid and granulocytic cells stimulated by G-CSF. Furthermore, G-CSF induced the growth of erythroid colonies from G-CSFR-expressing fetal liver cells from EPO receptor(-/-) (EPO-R-/-) or Stat5a(-/-) Stat5b(-/-) mice, demonstrating that erythroid differentiation can occur in the absence of EPO-R or Stat5. These data show that forced expression of G-CSFR allows G-CSF-dependent multilineage proliferation and differentiation of haematopoietic progenitors and rescues EPO-R-/- erythroid cells. While G-CSF induces Stat5 activation in G-CSFR-expressing erythroid cells, this activation is not necessary for the terminal erythroid differentiation induced by G-CSF.
引用
收藏
页码:449 / 458
页数:10
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