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, Tatsutoshi Nakahata

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4632-4640
Number of pages9
JournalBlood
Volume92
Issue number12
StatePublished - Dec 15 1998
Externally publishedYes

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Granulocyte Colony-Stimulating Factor Receptors
Granulocyte Colony-Stimulating Factor
Transgenic Mice
Bone
Interleukin-3
Cell culture
Fluorouracil
Spleen
Bone Marrow Cells
Cell Lineage
In Vitro Techniques
Mast Cells
Neutrophils
Clone Cells
Cell Culture Techniques

ASJC Scopus subject areas

  • Hematology

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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. / Yang, Feng Chun; Watanabe, Sumiko; Tsuji, Kohichiro; Xu, Ming Jiang; Kaneko, Azusa; Ebihara, Yasuhiro; Nakahata, Tatsutoshi.

In: Blood, Vol. 92, No. 12, 15.12.1998, p. 4632-4640.

Research output: Contribution to journalArticle

Yang, Feng Chun ; Watanabe, Sumiko ; Tsuji, Kohichiro ; Xu, Ming Jiang ; Kaneko, Azusa ; Ebihara, Yasuhiro ; Nakahata, Tatsutoshi. / 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. In: Blood. 1998 ; Vol. 92, No. 12. pp. 4632-4640.
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abstract = "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.",
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