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. 1993 Apr 15;90(8):3760–3764. doi: 10.1073/pnas.90.8.3760

Steel factor influences the distribution and activity of murine hematopoietic stem cells in vivo.

W H Fleming 1, E J Alpern 1, N Uchida 1, K Ikuta 1, I L Weissman 1
PMCID: PMC46381  PMID: 7682717

Abstract

To determine the effects of steel factor (SIF) on the number and distribution of phenotypically defined hematopoietic stem cells in vivo, mice were treated with continuous s.c. infusions of SIF for up to 7 days. The bone marrow demonstrated a transient 5-fold increase in the number of c-kit-positive lineage-negative/low cells with no change in cellularity. The radioprotective capacity of bone marrow cells was significantly reduced, and a 30% decrease in Thylo Lin-/lo Sca-1+ stem cells (Sca+ cells) was observed. In marked contrast, in the spleen a 2-fold increase in cellularity was accompanied by a 24-fold increase in c-kit-positive lineage-negative/low cells. SIF-treated spleen cells provided increased radioprotection and a corresponding 4-fold increase in the number of Sca+ cells. In the peripheral blood, an increase in both neutrophils and lymphocytes resulted; however, the number of c-kit-positive lineage-negative/low cells remained < 1%. SIF produced a 25-fold increase in radioprotection capacity and a 20-fold increase in the number of Sca+ cells in the peripheral blood. The increased radioprotection capacity of both the spleen cells and peripheral blood cells was associated with donor-derived, long-term multilineage reconstitution of recipient mice. The total number of Sca+ cells isolated per mouse after SIF treatment was not significantly increased. These results show that exogenous SIF treatment causes a redistribution of Sca+ cells and stem cell activity while having little effect on the total number of stem cells in the mouse.

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Selected References

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  1. Andrews R. G., Bartelmez S. H., Knitter G. H., Myerson D., Bernstein I. D., Appelbaum F. R., Zsebo K. M. A c-kit ligand, recombinant human stem cell factor, mediates reversible expansion of multiple CD34+ colony-forming cell types in blood and marrow of baboons. Blood. 1992 Aug 15;80(4):920–927. [PubMed] [Google Scholar]
  2. Andrews R. G., Bensinger W. I., Knitter G. H., Bartelmez S. H., Longin K., Bernstein I. D., Appelbaum F. R., Zsebo K. M. The ligand for c-kit, stem cell factor, stimulates the circulation of cells that engraft lethally irradiated baboons. Blood. 1992 Dec 1;80(11):2715–2720. [PubMed] [Google Scholar]
  3. Copeland N. G., Gilbert D. J., Cho B. C., Donovan P. J., Jenkins N. A., Cosman D., Anderson D., Lyman S. D., Williams D. E. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell. 1990 Oct 5;63(1):175–183. doi: 10.1016/0092-8674(90)90298-s. [DOI] [PubMed] [Google Scholar]
  4. Godin I., Deed R., Cooke J., Zsebo K., Dexter M., Wylie C. C. Effects of the steel gene product on mouse primordial germ cells in culture. Nature. 1991 Aug 29;352(6338):807–809. doi: 10.1038/352807a0. [DOI] [PubMed] [Google Scholar]
  5. Huang E., Nocka K., Beier D. R., Chu T. Y., Buck J., Lahm H. W., Wellner D., Leder P., Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell. 1990 Oct 5;63(1):225–233. doi: 10.1016/0092-8674(90)90303-v. [DOI] [PubMed] [Google Scholar]
  6. Ikuta K., Weissman I. L. Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1502–1506. doi: 10.1073/pnas.89.4.1502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Keshet E., Lyman S. D., Williams D. E., Anderson D. M., Jenkins N. A., Copeland N. G., Parada L. F. Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development. EMBO J. 1991 Sep;10(9):2425–2435. doi: 10.1002/j.1460-2075.1991.tb07782.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McNiece I. K., Langley K. E., Zsebo K. M. Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. Exp Hematol. 1991 Mar;19(3):226–231. [PubMed] [Google Scholar]
  9. Metcalf D., Nicola N. A. Direct proliferative actions of stem cell factor on murine bone marrow cells in vitro: effects of combination with colony-stimulating factors. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6239–6243. doi: 10.1073/pnas.88.14.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Migliaccio G., Migliaccio A. R., Valinsky J., Langley K., Zsebo K., Visser J. W., Adamson J. W. Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7420–7424. doi: 10.1073/pnas.88.16.7420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Molineux G., Migdalska A., Szmitkowski M., Zsebo K., Dexter T. M. The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor. Blood. 1991 Aug 15;78(4):961–966. [PubMed] [Google Scholar]
  12. Molineux G., Pojda Z., Hampson I. N., Lord B. I., Dexter T. M. Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor. Blood. 1990 Nov 15;76(10):2153–2158. [PubMed] [Google Scholar]
  13. Ogawa M., Matsuzaki Y., Nishikawa S., Hayashi S., Kunisada T., Sudo T., Kina T., Nakauchi H., Nishikawa S. Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med. 1991 Jul 1;174(1):63–71. doi: 10.1084/jem.174.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Okada S., Nakauchi H., Nagayoshi K., Nishikawa S., Nishikawa S., Miura Y., Suda T. Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. Blood. 1991 Oct 1;78(7):1706–1712. [PubMed] [Google Scholar]
  15. Rencricca N. J., Rizzoli V., Howard D., Duffy P., Stohlman F., Jr Stem cell migration and proliferation during severe anemia. Blood. 1970 Dec;36(6):764–771. [PubMed] [Google Scholar]
  16. Russell E. S. Hereditary anemias of the mouse: a review for geneticists. Adv Genet. 1979;20:357–459. [PubMed] [Google Scholar]
  17. Seifert M. F., Marks S. C., Jr The regulation of hemopoiesis in the spleen. Experientia. 1985 Feb 15;41(2):192–199. doi: 10.1007/BF02002613. [DOI] [PubMed] [Google Scholar]
  18. Spangrude G. J. Enrichment of murine haemopoietic stem cells: diverging roads. Immunol Today. 1989 Oct;10(10):344–350. doi: 10.1016/0167-5699(89)90192-8. [DOI] [PubMed] [Google Scholar]
  19. Spangrude G. J., Heimfeld S., Weissman I. L. Purification and characterization of mouse hematopoietic stem cells. Science. 1988 Jul 1;241(4861):58–62. doi: 10.1126/science.2898810. [DOI] [PubMed] [Google Scholar]
  20. Tsai M., Takeishi T., Thompson H., Langley K. E., Zsebo K. M., Metcalfe D. D., Geissler E. N., Galli S. J. Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6382–6386. doi: 10.1073/pnas.88.14.6382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tsuji K., Zsebo K. M., Ogawa M. Enhancement of murine blast cell colony formation in culture by recombinant rat stem cell factor, ligand for c-kit. Blood. 1991 Sep 1;78(5):1223–1229. [PubMed] [Google Scholar]
  22. Uchida N., Weissman I. L. Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin- Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow. J Exp Med. 1992 Jan 1;175(1):175–184. doi: 10.1084/jem.175.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ulich T. R., del Castillo J., McNiece I. K., Yi E. S., Alzona C. P., Yin S. M., Zsebo K. M. Stem cell factor in combination with granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF synergistically increases granulopoiesis in vivo. Blood. 1991 Oct 15;78(8):1954–1962. [PubMed] [Google Scholar]
  24. Vos O., Buurman W. A., Ploemacher R. E. Mobilization of haemopoietic stem cells (CFU) into the peripheral blood of the mouse; effects of endotoxin and other compounds. Cell Tissue Kinet. 1972 Nov;5(6):467–479. doi: 10.1111/j.1365-2184.1972.tb00385.x. [DOI] [PubMed] [Google Scholar]
  25. Williams N., Bertoncello I., Kavnoudias H., Zsebo K., McNiece I. Recombinant rat stem cell factor stimulates the amplification and differentiation of fractionated mouse stem cell populations. Blood. 1992 Jan 1;79(1):58–64. [PubMed] [Google Scholar]
  26. Zsebo K. M., Williams D. A., Geissler E. N., Broudy V. C., Martin F. H., Atkins H. L., Hsu R. Y., Birkett N. C., Okino K. H., Murdock D. C. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. 1990 Oct 5;63(1):213–224. doi: 10.1016/0092-8674(90)90302-u. [DOI] [PubMed] [Google Scholar]

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