Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors

Hiroaki Hisakawa, Daisuke Sugiyama, Ichiko Nishijima, Ming Jiang Xu, Hong Wu, Kazuki Nakao, Sumiko Watanabe, Motoya Katsuki, Shigetaka Asano, Ken Ichi Aral, Tatsutoshi Nakahata, Kohichiro Tsuji

Research output: Contribution to journalArticle

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Abstract

Although erythropoietin (EPO) and its receptor (EPOR) are crucial for the proliferation, survival, and terminal differentiation of erythroid progenitors, it remains to be elucidated whether EPOR-unique signaling is required for erythropoiesis. To address this issue, human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor (hGMR)-transgenic mice and heterozygous EPOR mutant mice were crossed by in vitro fertilization. In methylcellulose clonal culture of fetal liver (FL) cells of generated hGMR-expressing EPOR -/- embryos at embryonic day (E) 12.5 of gestation, hGM-CSF stimulated erythroid colony formation under serum-containing and serum-free conditions. Analysis of globin expression in individual erythrocyte-containing colonies formed from E12.5 FL cells showed that hGM-CSF supports primitive and definitive erythropoiesis even in EPOR -/- embryos. In comparison of activities between hGM-CSF and EPO in hGMR-expressing EPOR +/+ embryos, the 2 substances supported the formation of similar numbers of erythroid colonies in clonal culture of E12.5 FL cells; enhanced adult, but not embryonic, globin synthesis; and induced increase of GATA-1 expression and decrease of erythroid Kruppel-like factor and cMyb expression in the FL cells. On the other hand, in E8.0 yolk sac erythropoiesis, both substances had a similar effect on erythroid colony formation, but hGM-CSF induced an increase of β-major globin expression, while EPO did not. All together, the results of the present study demonstrated that hGM-CSF can stimulate the proliferation and differentiation of primitive and definitive erythroid cells independently of EPOR signal if they express hGMR, and the activity is comparable to that of EPO in definitive, but not primitive, erythropoiesis.

Original languageEnglish (US)
Pages (from-to)3618-3625
Number of pages8
JournalBlood
Volume98
Issue number13
DOIs
StatePublished - Dec 15 2001
Externally publishedYes

Fingerprint

Granulocyte-Macrophage Colony-Stimulating Factor Receptors
Erythropoietin Receptors
Erythropoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Colony-Stimulating Factor Receptors
Embryonic Structures
Liver
Globins
Erythropoietin
Yolk Sac
Erythroid Cells
Methylcellulose
Fertilization in Vitro
Serum
Human Activities
Transgenic Mice
Erythrocytes
Pregnancy
Survival

ASJC Scopus subject areas

  • Hematology

Cite this

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors. / Hisakawa, Hiroaki; Sugiyama, Daisuke; Nishijima, Ichiko; Xu, Ming Jiang; Wu, Hong; Nakao, Kazuki; Watanabe, Sumiko; Katsuki, Motoya; Asano, Shigetaka; Aral, Ken Ichi; Nakahata, Tatsutoshi; Tsuji, Kohichiro.

In: Blood, Vol. 98, No. 13, 15.12.2001, p. 3618-3625.

Research output: Contribution to journalArticle

Hisakawa, H, Sugiyama, D, Nishijima, I, Xu, MJ, Wu, H, Nakao, K, Watanabe, S, Katsuki, M, Asano, S, Aral, KI, Nakahata, T & Tsuji, K 2001, 'Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors', Blood, vol. 98, no. 13, pp. 3618-3625. https://doi.org/10.1182/blood.V98.13.3618
Hisakawa, Hiroaki ; Sugiyama, Daisuke ; Nishijima, Ichiko ; Xu, Ming Jiang ; Wu, Hong ; Nakao, Kazuki ; Watanabe, Sumiko ; Katsuki, Motoya ; Asano, Shigetaka ; Aral, Ken Ichi ; Nakahata, Tatsutoshi ; Tsuji, Kohichiro. / Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors. In: Blood. 2001 ; Vol. 98, No. 13. pp. 3618-3625.
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abstract = "Although erythropoietin (EPO) and its receptor (EPOR) are crucial for the proliferation, survival, and terminal differentiation of erythroid progenitors, it remains to be elucidated whether EPOR-unique signaling is required for erythropoiesis. To address this issue, human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor (hGMR)-transgenic mice and heterozygous EPOR mutant mice were crossed by in vitro fertilization. In methylcellulose clonal culture of fetal liver (FL) cells of generated hGMR-expressing EPOR -/- embryos at embryonic day (E) 12.5 of gestation, hGM-CSF stimulated erythroid colony formation under serum-containing and serum-free conditions. Analysis of globin expression in individual erythrocyte-containing colonies formed from E12.5 FL cells showed that hGM-CSF supports primitive and definitive erythropoiesis even in EPOR -/- embryos. In comparison of activities between hGM-CSF and EPO in hGMR-expressing EPOR +/+ embryos, the 2 substances supported the formation of similar numbers of erythroid colonies in clonal culture of E12.5 FL cells; enhanced adult, but not embryonic, globin synthesis; and induced increase of GATA-1 expression and decrease of erythroid Kruppel-like factor and cMyb expression in the FL cells. On the other hand, in E8.0 yolk sac erythropoiesis, both substances had a similar effect on erythroid colony formation, but hGM-CSF induced an increase of β-major globin expression, while EPO did not. All together, the results of the present study demonstrated that hGM-CSF can stimulate the proliferation and differentiation of primitive and definitive erythroid cells independently of EPOR signal if they express hGMR, and the activity is comparable to that of EPO in definitive, but not primitive, erythropoiesis.",
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AU - Hisakawa, Hiroaki

AU - Sugiyama, Daisuke

AU - Nishijima, Ichiko

AU - Xu, Ming Jiang

AU - Wu, Hong

AU - Nakao, Kazuki

AU - Watanabe, Sumiko

AU - Katsuki, Motoya

AU - Asano, Shigetaka

AU - Aral, Ken Ichi

AU - Nakahata, Tatsutoshi

AU - Tsuji, Kohichiro

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