title: Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation.
abstract: Multipotent murine stem cell lines (FDC-Pmix) depend on IL-3 for self-renewal and proliferation and can be induced to differentiate into multiple hematopoietic lineages. Single FDC-Pmix cells infected with retroviral vectors expressing GM-CSF are induced to differentiate into granulocytes and macrophages. This results in a complete loss of clonogenic cells if IL-3 is not exogenously supplied; however, multipotent variants can be selected that do not terminally differentiate if cells are kept in the presence of IL-3. Unidirectional and synchronous granulocyte and macrophage differentiation accompanied with loss of self-renewal capacity is induced when IL-3 is removed. Our data indicate that activation of the GM-CSF receptor induces differentiation of stem cells by an instructive mechanism that can be blocked by the activated IL-3 receptor. A model of how receptors can induce proliferation and cell-specific differentiation by two separate pathways is discussed.
authors.affiliation: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Federal Republic of Germany.
authors.forename: U
authors.initials: U
authors.lastname: Just
authors.forename: C
authors.initials: C
authors.lastname: Stocking
authors.forename: E
authors.initials: E
authors.lastname: Spooncer
authors.forename: T M
authors.initials: TM
authors.lastname: Dexter
authors.forename: W
authors.initials: W
authors.lastname: Ostertag
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006098:Granulocytes / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D007377:Interleukin-3 / Q000502:physiology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D009154:Mutation; D012190:Retroviridae
chemical_list: D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor