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Steel factor (c-kit ligand) promotes the survival of hematopoietic stem/progenitor cells in the absence of cell division. 1995

J R Keller, and M Ortiz, and F W Ruscetti
Biological Carcinogenesis and Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA.

It is known that the majority of primitive hematopoietic progenitors are in a noncycling quiescent state. In addition, normal hematopoietic progenitors and progenitor cell lines show an absolute dependence on growth factors for their survival in vitro, yet the effect of growth factors on progenitor cell survival has not been separated from effects on both proliferation and differentiation. Using an in vitro assay system, we examined whether growth factors could promote the survival of stem cells in culture in the absence of cell division. These studies show that steel factor (SLF) and, to a lesser extent, interleukin-3 (IL-3) directly promoted the survival of elutriated bone marrow progenitor cells (countercurrent centrifugal elutriation [CCE]-27) that are enriched for primitive hematopoietic progenitors that respond to the combination of SLF plus IL-3. Furthermore, SLF promoted the survival of short-term reconstituting cells (STRC), and long-term reconstituting cells (LTRC) with trilineage reconstitution potential in vivo. In comparison, granulocyte colony-stimulating factor (G-CSF), IL-6, leukemia inhibitory factor, IL-11, IL-1, granulocyte macrophage CSF (GM-CSF), and macrophage CSF (M-CSF) had no effect on the survival of these cells. In the presence of mitotic inhibitors (nocodazole or aphidicolin), SLF promoted the survival of CCE-27 progenitor cells that respond to the combination of SLF plus IL-3 in vitro and STRCs and LTRCs that are detected in vivo. Taken together, these data show that SLF can directly promote the survival of hematopoietic progenitor cells in the absence of cell division.

UI MeSH Term Description Entries
D007377 Interleukin-3 A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Burst-Promoting Factor, Erythrocyte,Colony-Stimulating Factor 2 Alpha,Colony-Stimulating Factor, Mast-Cell,Colony-Stimulating Factor, Multipotential,Erythrocyte Burst-Promoting Factor,IL-3,Mast-Cell Colony-Stimulating Factor,Multipotential Colony-Stimulating Factor,P-Cell Stimulating Factor,Eosinophil-Mast Cell Growth-Factor,Hematopoietin-2,Burst Promoting Factor, Erythrocyte,Colony Stimulating Factor, Mast Cell,Colony Stimulating Factor, Multipotential,Eosinophil Mast Cell Growth Factor,Erythrocyte Burst Promoting Factor,Hematopoietin 2,Interleukin 3,Multipotential Colony Stimulating Factor,P Cell Stimulating Factor
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002469 Cell Separation Techniques for separating distinct populations of cells. Cell Isolation,Cell Segregation,Isolation, Cell,Cell Isolations,Cell Segregations,Cell Separations,Isolations, Cell,Segregation, Cell,Segregations, Cell,Separation, Cell,Separations, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003115 Colony-Stimulating Factors Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include INTERLEUKIN-3; (IL-3); GRANULOCYTE COLONY-STIMULATING FACTOR; (G-CSF); MACROPHAGE COLONY-STIMULATING FACTOR; (M-CSF); and GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; (GM-CSF). MGI-1,Macrophage-Granulocyte Inducer,Colony Stimulating Factor,Colony-Stimulating Factor,MGI-1 Protein,Myeloid Cell-Growth Inducer,Protein Inducer MGI,Cell-Growth Inducer, Myeloid,Colony Stimulating Factors,Inducer, Macrophage-Granulocyte,Inducer, Myeloid Cell-Growth,MGI 1 Protein,MGI, Protein Inducer,Macrophage Granulocyte Inducer,Myeloid Cell Growth Inducer
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA

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