Human granulocyte colony-stimulating factor (G-CSF) stimulates the in vitro and in vivo development but not commitment of primitive multipotential progenitors from transgenic mice expressing the human G-CSF receptor.
Granulocyte colony-stimulating factor (G-CSF) stimulates the proliferation and restricted differentiation of hematopoietic progenitors into neutrophils. To clarify the effects of G-CSF on hematopoietic progenitors, we generated transgenic (Tg) mice that had ubiquitous expression of the human G-CSF receptor (hG-CSFR). In clonal cultures of bone marrow and spleen cells obtained from these mice, hG-CSF supported the growth of myelocytic as well as megakaryocytic, mast cell, mixed, and blast cell colonies. Single-cell cultures of lineage-negative (Lin-)c-Kit+Sca-1(+) or Sca-1(-) cells obtained from the Tg mice confirmed the direct effects of hG-CSF on the proliferation and differentiation of various progenitors. hG-CSF also had stimulatory effects on the formation of blast cell colonies in cultures using 5-fluorouracil-resistant hematopoietic progenitors and clone-sorted Lin-c-Kit+Sca-1(+) primitive hematopoietic cells. These colonies contained different progenitors in proportions similar to those obtained when mouse interleukin-3 was used in place of hG-CSF. Administration of hG-CSF to Tg mice led to significant increases in spleen colony-forming and mixed/blast cell colony-forming cells in bone marrow and spleen, but did not alter the proportion of myeloid progenitors in total clonogenic cells. These results show that, when functional G-CSFR is present on the cell surface, hG-CSF stimulates the development of primitive multipotential progenitors both in vitro and in vivo, but does not induce exclusive commitment to the myeloid lineage.
Yang
F C
FC
Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Watanabe
S
S
Tsuji
K
K
Xu
M J
MJ
Kaneko
A
A
Ebihara
Y
Y
Nakahata
T
T
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D011994:Recombinant Proteins; D013234:Stem Cells / Q000187:drug effects*
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005472:Fluorouracil