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Direct Induction of Hemogenic Endothelium and Blood by Overexpression of Transcription Factors in Human Pluripotent Stem Cells
Published on: December 3, 2015
Stem cell factor can stimulate the formation of eosinophils by two types of murine eosinophil progenitor cells
Donald Metcalf1, Sandra Mifsud, Ladina Di Rago
1Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. metcalf@wehi.edu.au
Abstract:
There are only three known stimuli for eosinophil formation-GM-CSF, interleukin-5 (IL-5), and IL-3. Because mice with inactivation of the gene encoding the common beta receptor chain for GM-CSF, IL-5, and IL-3 (betac(-/-) mice) cannot respond to GM-CSF or IL-5 and do not produce IL-3, they should lack eosinophils. However, they produce reduced numbers of eosinophils, indicating the existence of at least one additional stimulatory factor. Use of betac(-/-) mouse marrow cells failed to detect a novel eosinophil-stimulating factor in cell line- or organ-conditioned media, but stem cell factor (SCF) was found to have a previously unrecognized ability to stimulate the formation of eosinophil colonies or mixed neutrophil-eosinophil colonies. This action of SCF was also observable with marrow cells from other mouse strains and was enhanced by the addition of G-CSF but no other factor tested. Recloning of SCF-stimulated blast colonies showed that progenitors forming pure eosinophil or mixed neutrophil-eosinophil colonies can have a common ancestor but many appear to arise independently from different preprogenitor cells. The observed activity of SCF in marrow cultures was relatively weak, but its action may be stronger in vivo, and SCF needs to be added to GM-CSF, IL-5, and IL-3 in the list of cytokines able to stimulate eosinophil formation.
Insights
Stem cell factor (SCF) stimulates eosinophil formation, a previously unrecognized role. This finding expands the known list of cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5), and IL-3, that influence eosinophil production.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Eosinophil production is primarily stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5), and IL-3.
- Mice lacking the common beta receptor chain (betac(-/-)) for these cytokines should have no eosinophils but exhibit reduced numbers, suggesting other factors are involved.
Purpose of the Study:
- To identify novel factors that stimulate eosinophil formation.
- To investigate the role of stem cell factor (SCF) in eosinophil production.
Main Methods:
- Utilized betac(-/-) mouse marrow cells to screen for novel eosinophil-stimulating factors.
- Assessed the ability of stem cell factor (SCF) to induce eosinophil and mixed neutrophil-eosinophil colony formation in vitro.
- Analyzed progenitor cell origins using recloning of SCF-stimulated blast colonies.
Main Results:
- Stem cell factor (SCF) demonstrated an unrecognized ability to stimulate eosinophil and mixed neutrophil-eosinophil colony formation.
- SCF's effect was observed in multiple mouse strains and enhanced by G-CSF.
- SCF-stimulated progenitors can share common ancestors or arise independently.
Conclusions:
- Stem cell factor (SCF) is a novel cytokine that stimulates eosinophil formation, expanding the known list beyond GM-CSF, IL-5, and IL-3.
- SCF may play a more significant role in vivo than observed in vitro.
- The findings necessitate the inclusion of SCF in the list of cytokines regulating eosinophil production.
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