Self-Renewal of Haemopoietic Stem Cells: The Roles of the Environment, of Growth Factors and of the src Oncogene

  • T. M. Dexter
  • D. Boettiger
  • E. Spooncer
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 29)

Abstract

Haemopoietic stem cells are derived early in embryogenesis, are relatively few in number, but persist throughout adult life by virtue of their ability to undergo self-renewal. This ability to undergo self-renewal is a characteristic and essential property of stem cells: in the absence of self-renewal the haemopoietic system would rapidly decline, while excessive and persistent self-renewal (in the absence of death or differentiation) would lead to a dramatic reduction in the production of mature cells and an increase in primitive cells, i. e. a leukaemia [24, 35]. It follows, then, that an investigation of self-renewal and differentiation is an over-riding problem in the understanding of growth control in normal tissues as well as the lack of growth control which occurs during tumourigenesis. In this context, the role of tissue and cell lineage-restricted growth factors and of oncogenes (and their produets) is assuming more and more importance [16, 48]. In this communication, the role of one such growth factor (haemopoietic cell growth factor), the stromal cell milieu, and the src oncogene are discussed in relation to self-renewal and differentiation of haemopoietic cells.

Keywords

Agar Leukemia Recombination Radium Sarcoma 

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References

  1. 1.
    Allen TD, Dexter TM (1982) Ultrastructural aspects of erythropoietic differentiation in long-term bone marrow culture. Differentiation 21: 86–94PubMedCrossRefGoogle Scholar
  2. 2.
    Allen TD, Dexter TM (1983) Long term bone marrow cultures: an ultrastructural review. Scan Electron Microsc 4: 1851–1866Google Scholar
  3. 3.
    Anderson SM, Scolnick EM (1983) Construetion and isolation of a transforming murine retrovirus containing the sre gene of Rous sarcoma virus. J Virol 46: 594–605PubMedGoogle Scholar
  4. 4.
    Bazill GW, Haynes M, Garland J, Dexter TM (1983) Characterization and partial purification of a haemopoietic cell growth factor in Wehi-3 cell conditioned medium. Biochem J 210: 747–759PubMedGoogle Scholar
  5. 5.
    Beard JW (1963) Avian virus growths and their etiologic agents. Adv Cancer Res 7: 1–127PubMedCrossRefGoogle Scholar
  6. 6.
    Boettiger DB, Dexter TM (1984) Long-term marrow cultures in the analysis of viral leukemogenesis. Clin Haematol 13: 349–370PubMedGoogle Scholar
  7. 7.
    Boettiger DB, Anderson S, Dexter TM (1984) Effect of sre infection on long-term marrow cultures: Increased self-renewal of hemopoietic progenitor cells without leukemia. Cell 36: 763–773Google Scholar
  8. 8.
    Burgess AW, Camakaris J, Metealf D (1977) Purification and properties of colony-stimulating factor from mouse lung conditionedmedium. J Biol Chem 252: 1998–2003PubMedGoogle Scholar
  9. 9.
    Burgess AW, Metealf D, Rüssel SHM, Nicola NA (1980) Granulocyte/macrophage-megakaryocyte-, eosinophil-, and erythroidcolony- stimulating factors produced by mouse spieen cells. Biochem J 185: 301–314PubMedGoogle Scholar
  10. 10.
    Das SK, Stanley ER (1982) Structure-function studies of a colony stimulating factor (CSF-1). J Biol Chem 257: 13 579–13 684Google Scholar
  11. 11.
    Dexter TM (1982) Stromal cell associated haemopoiesis. J Cell Physiol [Suppl] 1: 87–94CrossRefGoogle Scholar
  12. 12.
    Dexter TM, Shadduck RK (1980) The regulation of haemopoiesis in long-term bone marrow cultures. I. Role of L-cell CSF. J Cell Physiol 102: 279–286Google Scholar
  13. 13.
    Dexter TM, Testa NG (1980) In vitro methods in haemopoiesis and lymphopoiesis.J Immunol Methods 38:177–190Google Scholar
  14. 14.
    Dexter TM, Allen TD, Lajtha LG (1977) Conditions Controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol 91: 335–344PubMedCrossRefGoogle Scholar
  15. 15.
    Dexter TM, Garland J, Scott D, Scolnick E, Metealf D (1980) Growth of factor dependent haemopoietic precursor cell lines. J Exp Med 152: 1036–1047PubMedCrossRefGoogle Scholar
  16. 16.
    Downward J, Yarden Y, Mayes F, Scrau G, Totty N, Stockwell P, Ullrich A, Sclessinger J, Waterfield MD (1984) Close similarity of epidermal growth factor reeeptor and V-erb- B oncogene protein sequences. Nature 307: 521–527PubMedCrossRefGoogle Scholar
  17. 17.
    Duesberg PH (1983) Retroviral transforming genes in normal cells. Nature 304: 219–226PubMedCrossRefGoogle Scholar
  18. 18.
    Eliason JF, Dexter TM, Testa N (1982) The regulation of hemopoiesis in long-term bone marrow cultures III. The role of burstpromoting activity. Exp Hemat 10: 444–450Google Scholar
  19. 19.
    Frindel E, Croizat H, Vassart F (1976) Stimulating factors liberated by treated bone marrow: In vitro effect on CFU kinetics. Exp Hemat 4: 56–61PubMedGoogle Scholar
  20. 20.
    Fung MC, Hapel AJ, Ymer S, Cohen DR, Johnson RM, Campbell HD, Young IG (1984) Molecular cloning of cDNA for murine interleukin-3. Nature 307: 233–237PubMedCrossRefGoogle Scholar
  21. 21.
    Greenberger JS, Eckner RJ, Sakakeeny M, Marks P, Reid D, Nabel G, Hapel A, Ihle JN, Humphries KC (1983) Interleukin 3-dependent hematopoietic progenitor cell lines. Fed Proc 42: 2762–2771PubMedGoogle Scholar
  22. 22.
    Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schräder JW, Palaszynski E, Dy M, Lebel B (1983) Biologie properties of homogeneous interleukin 3. J Immunol 131: 282–287PubMedGoogle Scholar
  23. 23.
    Iscove NN, Roitch CA, Williams N, Guilbert LJ (1982) Molecules stimulating early red cell, granulocyte/macrophage, and megakaryocyte precursors in culture: similarity in size, hydrophobicity and charge. J Cell Physiol [Suppl] 1: 23–30Google Scholar
  24. 24.
    Lajtha LG (1979) Stem cell concepts. Differentiation 4: 23–34CrossRefGoogle Scholar
  25. 25.
    Lajtha LG, Schofield R (1971) Regulation of stem cell renewal and differentiation: possible significance in ageing. In: Strehler BL (ed) Advances in gerontological research. Academic, New York, pp 131–146Google Scholar
  26. 26.
    Lictman MA (1981) The ultrastructure of the hemopoietic environment of the marrow: A review. Exp Hematol 9: 391–410Google Scholar
  27. 27.
    Lowenberg B, Dicke KA (1977) Induction of proliferation of haemopoietic stem cells in culture. Exp Hematol 5: 314–331Google Scholar
  28. 28.
    Metealf D (1977) Hemopoietic colonies. Springer, Berlin Heidelberg New York, p 227Google Scholar
  29. 29.
    Metealf D, Nicola NA (1983) Proliferative effects of purified granulocyte colony-stimulating factor ( G-CSF) on normal mouse haemopoietic cell. J Cell Physiol 116: 198–206Google Scholar
  30. 30.
    Metealf D, Johnson GR, Mandel TE (1979) Colony formation in agar by multipotential hemopoietic cells. J Cell Physiol 98: 401–424CrossRefGoogle Scholar
  31. 31.
    Metealf D, Johnson GR, Burgess AW (1980) Direct Stimulation by purified GM-CSF of the proliferation of multipotential and erythroid progenitor cells. Blood 55: 138–147Google Scholar
  32. 32.
    Nabel G, Galli SJ, Dvorak AM, Dvorak HF, Cantor H (1981) Inducer T-lymphocytes stimulate a factor that stimulates proliferation of cloned mast cells. Nature 291: 332–334PubMedCrossRefGoogle Scholar
  33. 33.
    Nicola NA, Metealf D, Matsumoto M, Johnson GR (1983) Purification of a factor inducing differentiation in murine myelomonocyte leukemia cells. J Biol Chem 258: 9017–9023PubMedGoogle Scholar
  34. 34.
    Schofield R, Dexter TM (1984) Studies on the self-renewal ability of CFU-S which have been serially transferred in long-term culture or in vivo. Leuk Res (in press)Google Scholar
  35. 35.
    Schofield R, Lajtha LG (1983) Determination of the probability of self-renewal in haemopoietic stem cells: a puzzle. Blood Cells 9: 467–473 (1983)Google Scholar
  36. 36.
    Schräder JW, Clark-Lewis I (1982) A T-cell derived factor stimulating multipotential hemopoietic stem cells: molecular weight and distinetion from T-cell growth factor and T-cell derived granulocyte macrophage colony-stimulating factor. J Immunol 129: 30–35PubMedGoogle Scholar
  37. 37.
    Shadduck RK, Waheed A, Greenberger JS, Dexter TM (1983) Production of colonystimulating factor in long-term bone-marrow cultures. J Cell Physiol 114: 88–92PubMedCrossRefGoogle Scholar
  38. 38.
    Shilo B, Weinberg RA (1981) DNA sequences homologous to vertebrate oncogenes are conserved in Drosophila melanogaster. Proc Natl Acad Sei USA 78: 6789–6792CrossRefGoogle Scholar
  39. 39.
    Siminovitch L, Till JE, McCulloch EA (1964) Decline in colony-forming ability of marrow cells subjected to serial transplantation into irradiated mice. J Cell Comp Physiol 64: 23–31CrossRefGoogle Scholar
  40. 40.
    Spooncer E, Gallagher JT, Krizsa F, Dexter TM (1983) Regulation of haemopoiesis in long term bone marrow cultures. IV. Glycosaminoglycan synthesis and the Stimulation of haemopoiesis by ß-D-xylosides. J Cell Biol 96: 510–514Google Scholar
  41. 41.
    Spooncer E, Boettiger DB, Dexter TM (1984) Continuous in vitro generation of clonogenic multipotential stem cells from src infected cultures. Nature (in press)Google Scholar
  42. 42.
    Stanley ER (1979) Colony stimulating factor (CSF) radioimmunoassay: Detection of a CSF subclass stimulating macrophage production. Proc Natl Acad Sei USA 76: 2969–2973CrossRefGoogle Scholar
  43. 43.
    Tatchell K, Chaleff DT, Defeo-Jones D, Scolnick EM (1984) Requirement of either of a pair of ras-related genes of saccharomyces cerevisiae for spore viability. Nature 309: 523 - 527PubMedCrossRefGoogle Scholar
  44. 44.
    Tertian G, Yung TP, Guy-Grand D, Moore MAS (1981) Long term in vitro culture of murine mast cells. I. Description of a growth factor-dependent culture technique. J Immunol 127: 788–794Google Scholar
  45. 45.
    Toksoz D (1980) Ph.D. Thesis, University of ManchesterGoogle Scholar
  46. 46.
    Toksoz D, Dexter TM, Lord BI, Wright EG, Lajtha LG (1980) The regulation of hemopoiesis in long-term bone marrow cultures. II. Stimulation and inhibition of stem cell proliferation. Blood 55: 931–936Google Scholar
  47. 47.
    Wagemaker G, Peters MF (1978) Effects of human leukocyte conditioned medium on mouse haemopoietic progenitor cells. Cell Tissue Kinet 11: 45–56PubMedGoogle Scholar
  48. 48.
    Waterfield MD, Scrace GT, Whittle N, Stroobart D, Johnsson A, Wasterson A, WestermarkB, Heldin CM, Huang JS, Duel TF (1983) Platelet derived growth factor is structurally related to the putative transforming protein of p28 sis of Simian sarcoma virus. Nature 304: 35–39Google Scholar
  49. 49.
    Weiss L (1981) Haematopoiesis in mammalian bone marrow. In: Porter R, Whelan J (eds) Cell interactions in haemopoietic differentiation. Ciba Foundation Symposium 84. Pitman Medical, Tunbridge Wells, pp 1 - 4Google Scholar
  50. 50.
    Williams N, Burgess AW (1980) The effect of mouse lung granulocyte macrophage colony stimulating factors and other colony stimulating activities on the proliferation and differentiation of murine bone marrow cells in long-term cultures. J Cell Physiol 102: 287–295PubMedCrossRefGoogle Scholar
  51. 51.
    Williams N, Jackson H, Rabellino E (1977) Proliferation and differentiation of normal granulopoietic cells in continuous bone marrow cultures. J Cell Physiol 93: 435–440PubMedCrossRefGoogle Scholar
  52. 52.
    Wright EG, Lord BI (1977) Regulation of CFU-S proliferation by locally produced endogenous factors. Biomed Express 27: 215–218Google Scholar
  53. 53.
    Wright EG, Garland JM, Lord BI (1980) Specific inhibition of haemopoietic stem cell proliferation: characterization of inhibitor producing cells. Leuk Res 4: 537–545PubMedCrossRefGoogle Scholar
  54. 54.
    Wright EG, Ali AM, Riehes AC, Lord BI (1982) Stimulation of haemopoietic stem cell proliferation: characteristics of stimulator producing cells. Leuk Res 6: 531–539PubMedCrossRefGoogle Scholar
  55. 55.
    Yokota T, Lee F, Rennick D, Hall C, Arai N, Mosmann T, Nabel G, Cantor H, Arai K (1984) Isolation and characterization of a full-length cDNA for mast cell growth factor from a mouse T-cell clone: expression in monkey cells. Proc Nat Acad Si USA 81: 1070–1074CrossRefGoogle Scholar
  56. 56.
    Yung YP, Eger R, Tertian G, Moore MAS (1981) Long-term in vitro culture of murine mast cells. II. Purification of a mast cell growth factor and its dissociation from TCGF. J Immunol 127: 794–799Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • T. M. Dexter
    • 1
  • D. Boettiger
    • 2
  • E. Spooncer
    • 1
  1. 1.Department of Experimental Haematology, Paterson LaboratoriesChristie Hospital & Holt Radium InstituteWithington, ManchesterEngland
  2. 2.Department of MicrobiologyUniversity of PennsylvaniaUSA

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