Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Aug 15;88(16):7420–7424. doi: 10.1073/pnas.88.16.7420

Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells.

G Migliaccio 1, A R Migliaccio 1, J Valinsky 1, K Langley 1, K Zsebo 1, J W Visser 1, J W Adamson 1
PMCID: PMC52307  PMID: 1714603

Abstract

Recombinant rat stem cell factor (SCF) was studied for its ability to stimulate the growth of murine hematopoietic progenitor cells and to generate colony-forming cells (CFC) from highly enriched populations of hematopoietic cells. In serum-deprived cultures, SCF alone stimulated few colonies but interacted with a number of other hematopoietic growth factors, particularly interleukin 3, to promote colony formation. The most marked effect was on the generation of mixed-cell colonies. Hematopoietic cells were sorted into wheat-germ agglutinin-negative, monocyte-depleted, rhodamine 123 (Rh123)-bright or Rh123-dull cells. Historically, Rh123-bright cells are capable of short-term (less than 1 mo) marrow engraftment, whereas among Rh123-dull cells are cells capable of long-term marrow engraftment. Enriched cells (2.5 x 10(3) were placed into serum-deprived liquid cultures with various hematopoietic growth factors. Initially, the Rh123-bright and Rh123-dull cells had few CFC but, in the presence of interleukin 3 and SCF, Rh123-bright cells gave rise to greater than 15,000 granulocyte/macrophage CFC, greater than 1500 erythroid burst-forming cells, and greater than 700 mixed-cell CFC by day 5. In contrast, Rh123-dull cells proliferated only in the presence of interleukin 3 and SCF, but total cell numbers rose to a peak of 18,000 by day 21, and one-third of the cells were CFC. Thus, SCF, in combination with other growth factors, can generate large numbers of CFC from pre-CFC and appears to act earlier than hematopoietic growth factors described to date.

Full text

PDF
7420

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berenson R. J., Andrews R. G., Bensinger W. I., Kalamasz D., Knitter G., Buckner C. D., Bernstein I. D. Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest. 1988 Mar;81(3):951–955. doi: 10.1172/JCI113409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Broxmeyer H. E., Hangoc G., Cooper S., Anderson D., Cosman D., Lyman S. D., Williams D. E. Influence of murine mast cell growth factor (c-kit ligand) on colony formation by mouse marrow hematopoietic progenitor cells. Exp Hematol. 1991 Feb;19(2):143–146. [PubMed] [Google Scholar]
  3. Cross M., Dexter T. M. Growth factors in development, transformation, and tumorigenesis. Cell. 1991 Jan 25;64(2):271–280. doi: 10.1016/0092-8674(91)90638-f. [DOI] [PubMed] [Google Scholar]
  4. Dexter T. M., Heyworth C. M., Spooncer E., Ponting I. L. The role of growth factors in self-renewal and differentiation of haemopoietic stem cells. Philos Trans R Soc Lond B Biol Sci. 1990 Mar 12;327(1239):85–98. doi: 10.1098/rstb.1990.0045. [DOI] [PubMed] [Google Scholar]
  5. Flanagan J. G., Leder P. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell. 1990 Oct 5;63(1):185–194. doi: 10.1016/0092-8674(90)90299-t. [DOI] [PubMed] [Google Scholar]
  6. Hodgson G. S., Bradley T. R. Properties of haematopoietic stem cells surviving 5-fluorouracil treatment: evidence for a pre-CFU-S cell? Nature. 1979 Oct 4;281(5730):381–382. doi: 10.1038/281381a0. [DOI] [PubMed] [Google Scholar]
  7. Ikebuchi K., Wong G. G., Clark S. C., Ihle J. N., Hirai Y., Ogawa M. Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035–9039. doi: 10.1073/pnas.84.24.9035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Iscove N. N., Yan X. Q. Precursors (pre-CFCmulti) of multilineage hemopoietic colony-forming cells quantitated in vitro. Uniqueness of IL-1 requirement, partial separation from pluripotential colony-forming cells, and correlation with long term reconstituting cells in vivo. J Immunol. 1990 Jul 1;145(1):190–195. [PubMed] [Google Scholar]
  9. Johnson L. V., Walsh M. L., Bockus B. J., Chen L. B. Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy. J Cell Biol. 1981 Mar;88(3):526–535. doi: 10.1083/jcb.88.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jones R. J., Wagner J. E., Celano P., Zicha M. S., Sharkis S. J. Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells. Nature. 1990 Sep 13;347(6289):188–189. doi: 10.1038/347188a0. [DOI] [PubMed] [Google Scholar]
  11. Martin F. H., Suggs S. V., Langley K. E., Lu H. S., Ting J., Okino K. H., Morris C. F., McNiece I. K., Jacobsen F. W., Mendiaz E. A. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell. 1990 Oct 5;63(1):203–211. doi: 10.1016/0092-8674(90)90301-t. [DOI] [PubMed] [Google Scholar]
  12. Matsui Y., Zsebo K. M., Hogan B. L. Embryonic expression of a haematopoietic growth factor encoded by the Sl locus and the ligand for c-kit. Nature. 1990 Oct 18;347(6294):667–669. doi: 10.1038/347667a0. [DOI] [PubMed] [Google Scholar]
  13. Micklem H. S., Lennon J. E., Ansell J. D., Gray R. A. Numbers and dispersion of repopulating hematopoietic cell clones in radiation chimeras as functions of injected cell dose. Exp Hematol. 1987 Mar;15(3):251–257. [PubMed] [Google Scholar]
  14. Migliaccio A. R., Visser J. W. Proliferation of purified murine hemopoietic stem cells in serum-free cultures stimulated with purified stem-cell-activating factor. Exp Hematol. 1986 Dec;14(11):1043–1048. [PubMed] [Google Scholar]
  15. Migliaccio G., Migliaccio A. R. Cloning of human erythroid progenitors (BFU-E) in the absence of fetal bovine serum. Br J Haematol. 1987 Oct;67(2):129–133. doi: 10.1111/j.1365-2141.1987.tb02315.x. [DOI] [PubMed] [Google Scholar]
  16. Migliaccio G., Migliaccio A. R. Early hemopoietic differentiation: the action of multi-CSF is complemented by lineage specific growth factors. Ann N Y Acad Sci. 1987;511:39–49. doi: 10.1111/j.1749-6632.1987.tb36236.x. [DOI] [PubMed] [Google Scholar]
  17. Migliaccio G., Migliaccio A. R., Kaushansky K., Adamson J. W. Regulation of differentiation of murine progenitor cells derived from blast cell colonies under serum-deprived conditions. Exp Hematol. 1989 Feb;17(2):110–115. [PubMed] [Google Scholar]
  18. Migliaccio G., Migliaccio A. R., Visser J. W. Synergism between erythropoietin and interleukin-3 in the induction of hematopoietic stem cell proliferation and erythroid burst colony formation. Blood. 1988 Sep;72(3):944–951. [PubMed] [Google Scholar]
  19. Müller-Sieburg C. E., Townsend K., Weissman I. L., Rennick D. Proliferation and differentiation of highly enriched mouse hematopoietic stem cells and progenitor cells in response to defined growth factors. J Exp Med. 1988 Jun 1;167(6):1825–1840. doi: 10.1084/jem.167.6.1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nocka K., Buck J., Levi E., Besmer P. Candidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. EMBO J. 1990 Oct;9(10):3287–3294. doi: 10.1002/j.1460-2075.1990.tb07528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Spangrude G. J., Johnson G. R. Resting and activated subsets of mouse multipotent hematopoietic stem cells. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7433–7437. doi: 10.1073/pnas.87.19.7433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Visser J. W., Bauman J. G., Mulder A. H., Eliason J. F., de Leeuw A. M. Isolation of murine pluripotent hemopoietic stem cells. J Exp Med. 1984 Jun 1;159(6):1576–1590. doi: 10.1084/jem.159.6.1576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Visser J. W., De Vries P. Identification and purification of murine hematopoietic stem cells by flow cytometry. Methods Cell Biol. 1990;33:451–468. [PubMed] [Google Scholar]
  25. Visser J. W., Van Bekkum D. W. Purification of pluripotent hemopoietic stem cells: past and present. Exp Hematol. 1990 Mar;18(3):248–256. [PubMed] [Google Scholar]
  26. Visser J. W., de Vries P. Isolation of spleen-colony forming cells (CFU-s) using wheat germ agglutinin and rhodamine 123 labeling. Blood Cells. 1988;14(2-3):369–384. [PubMed] [Google Scholar]
  27. Williams D. E., Eisenman J., Baird A., Rauch C., Van Ness K., March C. J., Park L. S., Martin U., Mochizuki D. Y., Boswell H. S. Identification of a ligand for the c-kit proto-oncogene. Cell. 1990 Oct 5;63(1):167–174. doi: 10.1016/0092-8674(90)90297-r. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. van der Sluijs J. P., de Jong J. P., Brons N. H., Ploemacher R. E. Marrow repopulating cells, but not CFU-S, establish long-term in vitro hemopoiesis on a marrow-derived stromal layer. Exp Hematol. 1990 Sep;18(8):893–896. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES