FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver

M. O. Muench, M. G. Roncarolo, S. Menon, Y. Xu, R. Kastelein, S. Zurawski, C. H. Hannum, J. Culpepper, F. Lee, R. Namikawa

Research output: Contribution to journalArticle

Abstract

The effects of the recently identified FLK-2/FLT-3 ligand (FL) on the growth of purified human fetal liver progenitors were investigated under serum-deprived culture conditions. FL alone was found to stimulate modest proliferation in short-term cultures of CD34++ CD38+ lineage (Lin)- light-density fetal liver (LDFL) cells and the more primitive CD34++ CD38- Lin- LDFL cells. However, the low levels of growth induced by FL were insufficient for colony formation in clonal cultures. Synergism between FL and either granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or KIT ligand (KL) was observed in promoting the growth of high-proliferative potential (HPP) colony-forming cells (CFC) and/or low- proliferative potential (LPP)-CFC in cultures of CD34++ CD38+ Lin- and CD34++ CD38- Lin- LDFL-cells. FL, alone or in combination with other cytokines, was not found to affect the growth of CD34+ Lin- LDFL cells, the most mature subpopulation of fetal liver progenitors investigated. The growth of the most primitive subset of progenitors studied, CD34++ CD38- Lin- LDFL cells, required the interactions of at least two cytokines, because only very low levels of growth were observed in response to either FL, GM-CSF, IL- 3 or KL alone. However, the results of delayed cytokine-addition experiments suggested that individually these cytokines did promote the survival of this early population of progenitors. Although two-factor combinations of FL, KL, and GM-CSF were observed to promote the growth of early progenitors in a synergistic manner, neither of these factors was found to make fetal liver progenitors more responsive to suboptimal concentrations of a second cytokine. Only myeloid cells were recovered from liquid cultures of CD34++ CD38- Lin- LDFL cells grown in the presence of combinations of FL, KL, and GM-CSF. These results indicate that FL is part of a network of growth factors that regulate the growth and survival of early hematopoietic progenitors.

Original languageEnglish
Pages (from-to)963-972
Number of pages10
JournalBlood
Volume85
Issue number4
Publication statusPublished - 1995

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Liver
Ligands
Growth
Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines
Interleukin-3
Light
Myeloid Cells
Cell culture
Cell Communication
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Muench, M. O., Roncarolo, M. G., Menon, S., Xu, Y., Kastelein, R., Zurawski, S., ... Namikawa, R. (1995). FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver. Blood, 85(4), 963-972.

FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver. / Muench, M. O.; Roncarolo, M. G.; Menon, S.; Xu, Y.; Kastelein, R.; Zurawski, S.; Hannum, C. H.; Culpepper, J.; Lee, F.; Namikawa, R.

In: Blood, Vol. 85, No. 4, 1995, p. 963-972.

Research output: Contribution to journalArticle

Muench, MO, Roncarolo, MG, Menon, S, Xu, Y, Kastelein, R, Zurawski, S, Hannum, CH, Culpepper, J, Lee, F & Namikawa, R 1995, 'FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver', Blood, vol. 85, no. 4, pp. 963-972.
Muench MO, Roncarolo MG, Menon S, Xu Y, Kastelein R, Zurawski S et al. FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver. Blood. 1995;85(4):963-972.
Muench, M. O. ; Roncarolo, M. G. ; Menon, S. ; Xu, Y. ; Kastelein, R. ; Zurawski, S. ; Hannum, C. H. ; Culpepper, J. ; Lee, F. ; Namikawa, R. / FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver. In: Blood. 1995 ; Vol. 85, No. 4. pp. 963-972.
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abstract = "The effects of the recently identified FLK-2/FLT-3 ligand (FL) on the growth of purified human fetal liver progenitors were investigated under serum-deprived culture conditions. FL alone was found to stimulate modest proliferation in short-term cultures of CD34++ CD38+ lineage (Lin)- light-density fetal liver (LDFL) cells and the more primitive CD34++ CD38- Lin- LDFL cells. However, the low levels of growth induced by FL were insufficient for colony formation in clonal cultures. Synergism between FL and either granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or KIT ligand (KL) was observed in promoting the growth of high-proliferative potential (HPP) colony-forming cells (CFC) and/or low- proliferative potential (LPP)-CFC in cultures of CD34++ CD38+ Lin- and CD34++ CD38- Lin- LDFL-cells. FL, alone or in combination with other cytokines, was not found to affect the growth of CD34+ Lin- LDFL cells, the most mature subpopulation of fetal liver progenitors investigated. The growth of the most primitive subset of progenitors studied, CD34++ CD38- Lin- LDFL cells, required the interactions of at least two cytokines, because only very low levels of growth were observed in response to either FL, GM-CSF, IL- 3 or KL alone. However, the results of delayed cytokine-addition experiments suggested that individually these cytokines did promote the survival of this early population of progenitors. Although two-factor combinations of FL, KL, and GM-CSF were observed to promote the growth of early progenitors in a synergistic manner, neither of these factors was found to make fetal liver progenitors more responsive to suboptimal concentrations of a second cytokine. Only myeloid cells were recovered from liquid cultures of CD34++ CD38- Lin- LDFL cells grown in the presence of combinations of FL, KL, and GM-CSF. These results indicate that FL is part of a network of growth factors that regulate the growth and survival of early hematopoietic progenitors.",
author = "Muench, {M. O.} and Roncarolo, {M. G.} and S. Menon and Y. Xu and R. Kastelein and S. Zurawski and Hannum, {C. H.} and J. Culpepper and F. Lee and R. Namikawa",
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AU - Muench, M. O.

AU - Roncarolo, M. G.

AU - Menon, S.

AU - Xu, Y.

AU - Kastelein, R.

AU - Zurawski, S.

AU - Hannum, C. H.

AU - Culpepper, J.

AU - Lee, F.

AU - Namikawa, R.

PY - 1995

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N2 - The effects of the recently identified FLK-2/FLT-3 ligand (FL) on the growth of purified human fetal liver progenitors were investigated under serum-deprived culture conditions. FL alone was found to stimulate modest proliferation in short-term cultures of CD34++ CD38+ lineage (Lin)- light-density fetal liver (LDFL) cells and the more primitive CD34++ CD38- Lin- LDFL cells. However, the low levels of growth induced by FL were insufficient for colony formation in clonal cultures. Synergism between FL and either granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or KIT ligand (KL) was observed in promoting the growth of high-proliferative potential (HPP) colony-forming cells (CFC) and/or low- proliferative potential (LPP)-CFC in cultures of CD34++ CD38+ Lin- and CD34++ CD38- Lin- LDFL-cells. FL, alone or in combination with other cytokines, was not found to affect the growth of CD34+ Lin- LDFL cells, the most mature subpopulation of fetal liver progenitors investigated. The growth of the most primitive subset of progenitors studied, CD34++ CD38- Lin- LDFL cells, required the interactions of at least two cytokines, because only very low levels of growth were observed in response to either FL, GM-CSF, IL- 3 or KL alone. However, the results of delayed cytokine-addition experiments suggested that individually these cytokines did promote the survival of this early population of progenitors. Although two-factor combinations of FL, KL, and GM-CSF were observed to promote the growth of early progenitors in a synergistic manner, neither of these factors was found to make fetal liver progenitors more responsive to suboptimal concentrations of a second cytokine. Only myeloid cells were recovered from liquid cultures of CD34++ CD38- Lin- LDFL cells grown in the presence of combinations of FL, KL, and GM-CSF. These results indicate that FL is part of a network of growth factors that regulate the growth and survival of early hematopoietic progenitors.

AB - The effects of the recently identified FLK-2/FLT-3 ligand (FL) on the growth of purified human fetal liver progenitors were investigated under serum-deprived culture conditions. FL alone was found to stimulate modest proliferation in short-term cultures of CD34++ CD38+ lineage (Lin)- light-density fetal liver (LDFL) cells and the more primitive CD34++ CD38- Lin- LDFL cells. However, the low levels of growth induced by FL were insufficient for colony formation in clonal cultures. Synergism between FL and either granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or KIT ligand (KL) was observed in promoting the growth of high-proliferative potential (HPP) colony-forming cells (CFC) and/or low- proliferative potential (LPP)-CFC in cultures of CD34++ CD38+ Lin- and CD34++ CD38- Lin- LDFL-cells. FL, alone or in combination with other cytokines, was not found to affect the growth of CD34+ Lin- LDFL cells, the most mature subpopulation of fetal liver progenitors investigated. The growth of the most primitive subset of progenitors studied, CD34++ CD38- Lin- LDFL cells, required the interactions of at least two cytokines, because only very low levels of growth were observed in response to either FL, GM-CSF, IL- 3 or KL alone. However, the results of delayed cytokine-addition experiments suggested that individually these cytokines did promote the survival of this early population of progenitors. Although two-factor combinations of FL, KL, and GM-CSF were observed to promote the growth of early progenitors in a synergistic manner, neither of these factors was found to make fetal liver progenitors more responsive to suboptimal concentrations of a second cytokine. Only myeloid cells were recovered from liquid cultures of CD34++ CD38- Lin- LDFL cells grown in the presence of combinations of FL, KL, and GM-CSF. These results indicate that FL is part of a network of growth factors that regulate the growth and survival of early hematopoietic progenitors.

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