Premium
The granulocyte colony‐stimulating factor receptor supports erythroid differentiation in the absence of the erythropoietin receptor or Stat5
Author(s) -
Millot Gaël A.,
Svinarchuk Fédor,
Lacout Catherine,
Vainchenker William,
Dumenil Dominique
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02591.x
Subject(s) - granulocyte colony stimulating factor receptor , haematopoiesis , erythropoietin , erythropoietin receptor , biology , erythropoiesis , granulocyte macrophage colony stimulating factor receptor , stat5 , stem cell factor , interleukin 3 , microbiology and biotechnology , progenitor cell , megakaryocyte , receptor , signal transduction , stem cell , medicine , endocrinology , immunology , macrophage colony stimulating factor , macrophage , t cell , biochemistry , anemia , interleukin 21 , in vitro , immune system
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.