Skip to main content

Insertional Mutagenesis as a Route to Identifying Genes Involved in Self Renewal of Haemopoietic Stem Cells

  • Conference paper
Lymphoid Organogenesis

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 251))

Summary

The genes controlling self renewal in the haemopoietic system are still unknown. Using retroviral insertional mutagenesis we have established multipotent haemopoietic stem cell lines (FDCP-mix) that possess an increased self renewal capacity in vitro. To identify genes involved in the regulation of self renewal, proviral integration sites were cloned from FDCP-mix cells and used as probes to screen independently isolated FDCP-mix cell lines for a common proviral insertion site. So far, two common integration sites have been identified, A25 and M4. A25 is rearranged in 50% of the FDCP-mix cell lines and M4 in 10%. Genes located at or near these sites are likely candidates for the control of self renewal of haemopoietic stem cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Boettiger D, Anderson S, Dexter M (1984) Effect of src infection on long-term marrow cultures: increased self-renewal of hemopoietic progenitor cells without leukemia. Cell 36:763-773

    Article  PubMed  CAS  Google Scholar 

  • Ford A, Healy L, Bennett A, Navarro E, Spooncer E, Greaves M (1992) Multilineage phenotype of interleukin-3-dependent progenitor cells. Blood 79:1962-1971

    PubMed  CAS  Google Scholar 

  • Hagenaars C, Kawilarang de Haas E, van der Kraan A, Spooncer E, Dexter M, Nijweide P (1991) Interleukin-3-dependent hematopoietic stem cell lines capable of osteoclast formation in vitro. J. Bone Miner. Res. 6:947-954

    Article  PubMed  CAS  Google Scholar 

  • Heyworth C, Dexter M, Kan O, Whetton A (1990) The role of hemopoietic growth factors in self-renewal and differentiation of IL-3-dependent multipotential stem cells. Growth Factors 2:297-211

    Article  Google Scholar 

  • Heyworth C, Alauldin M, Cross M, Fairbairn L, Dexter M (1995) Erythroid development of the FDCP-mix A4 multipotent cell line is governed by relative concentrations of erythropoietin and interleukin 3. Br. J. Haematol. 91:15-22

    Article  PubMed  CAS  Google Scholar 

  • Jonkers J, Berns A (1996) Retroviral insertional mutagenesis as a strategy to identify cancer genes. Biochim. Biophys. Acta 1287:29-57

    Google Scholar 

  • Just U, Stocking C, Spooncer E, Dexter M, Ostertag W (1991) Expression of the GM-C SF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation. Cell 64:1163-1173

    Article  PubMed  CAS  Google Scholar 

  • Just U, Katsuno M, Stocking C, Spooncer E, Dexter M (1993) Targeted in vivo infection with a retroviral vector carrying the Interleukin-3 (Multi-C SF) gene leads to immortalization and leukemic transformation of primitive hematopoietic progenitor cells. Growth Factors 9:41-55

    Article  PubMed  CAS  Google Scholar 

  • Lock L, Jenkins N, Copeland N (1991) Mutagenesis of the mouse germline using retroviruses. Curr. Top. Microbiol. Immunol. 171:27-41

    Article  PubMed  CAS  Google Scholar 

  • Spooncer E, Boettiger D, Dexter M (1984) Continuous in vitro generation of multipotent stem cell clones from src-infected cultures. Nature 310:228-230

    Article  PubMed  CAS  Google Scholar 

  • Spooncer E, Heyworth CM, Dunn A, Dexter M (1986) Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors. Differentiation 31:111-118

    Article  PubMed  CAS  Google Scholar 

  • Stoye J, Coffin J (1987) The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination. J. Virol. 61:2659-2669

    PubMed  CAS  Google Scholar 

  • Wyke J, Stoker A, Searle S, Spooncer E, Simmons P, Dexter M (1986) Perturbed hemopoiesis and the generation of multipotential cell clones in src-infected bone marrow cultures is an indirect or transient effect of the oncogene. Mol. Cell. Biol. 6:959-963

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Just, U., Boettiger, D., Kan, O., Dexter, T.M., Spooncer, E. (2000). Insertional Mutagenesis as a Route to Identifying Genes Involved in Self Renewal of Haemopoietic Stem Cells. In: Melchers, F. (eds) Lymphoid Organogenesis. Current Topics in Microbiology and Immunology, vol 251. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57276-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-57276-0_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63186-3

  • Online ISBN: 978-3-642-57276-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics