Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation.
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.
Just
U
U
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Federal Republic of Germany.
Stocking
C
C
Spooncer
E
E
Dexter
T M
TM
Ostertag
W
W
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
D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor