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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4632-4640
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
Feng-Chun Yang,
Sumiko Watanabe,
Kohichiro Tsuji,
Ming-jiang Xu,
Azusa Kaneko,
Yasuhiro Ebihara, and
Tatsutoshi Nakahata
From the Department of Clinical Oncology, the Department of Molecular
and Developmental Biology, The Institute of Medical Science, The
University of Tokyo, Tokyo, Japan.
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
Linc-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.
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