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Stem Cells

Generation and characterization of a novel hematopoietic progenitor cell line with DC differentiation potential

Leukemia volume 20, pages 870–876 (2006)Cite this article

A Correction to this article was published on 19 April 2021

A Correction to this article was published on 27 January 2021

A Corrigendum to this article was published on 10 October 2012

This article has been updated

Abstract

Studies of hematopoietic stem cell (HSC)-derived dendritic cells (DCs) are often limited by the rarity of HSC. To facilitate the study of DCs, we have generated a novel cell line (CR1) by retroviral NotchIC gene transfer into Sca1+ckit+lin− HSC. CR1 cells proliferated in vitro in the presence of recombinant interleukin-3. They maintained an immature progenitor cell phenotype and an intact karyotype. In the presence of granulocyte–macrophage colony-stimulating factor or Flt3L, CR1 cells differentiated into myeloid and plasmacytoid DCs, respectively. Functionally, CR1 cells were comparable to primary bone-marrow-derived DCs with respect to Toll-like-receptor-mediated maturation, cytokine release and capacity to induce effective antitumor immunity. CR1 cells thus provide an elegant new cellular tool to study DC development, function and preclinical DC-based immunotherapies.

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References

  1. Banchereau J, Palucka AK . Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 2005; 5: 296–306.

    Article  CAS  Google Scholar 

  2. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ . Dendritic cell immunotherapy: mapping the way. Nat Med 2004; 10: 475–480.

    Article  CAS  Google Scholar 

  3. Tsai S, Bartelmez S, Sitnicka E, Collins S . Lymphohematopoietic progenitors immortalized by a retroviral vector harboring a dominant-negative retinoic acid receptor can recapitulate lymphoid, myeloid, and erythroid development. Genes Dev 1994; 8: 2831–2841.

    Article  CAS  Google Scholar 

  4. Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 2000; 6: 1278–1281.

    Article  CAS  Google Scholar 

  5. Krosl J, Austin P, Beslu N, Kroon E, Humphries RK, Sauvageau G . In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein. Nat Med 2003; 9: 1428–1432.

    Article  CAS  Google Scholar 

  6. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 2003; 423: 409–414.

    Article  CAS  Google Scholar 

  7. Maillard I, Fang T, Pear WS . Regulation of lymphoid development, differentiation, and function by the Notch pathway. Annu Rev Immunol 2005; 23: 945–974.

    Article  CAS  Google Scholar 

  8. Kawamata S, Du C, Li K, Lavau C . Notch1 perturbation of hemopoiesis involves non-cell-autonomous modifications. J Immunol 2002; 168: 1738–1745.

    Article  CAS  Google Scholar 

  9. Lam LT, Ronchini C, Norton J, Capobianco AJ, Bresnick EH . Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by Notch-1. J Biol Chem 2000; 275: 19676–19684.

    Article  CAS  Google Scholar 

  10. Ishiko E, Matsumura I, Ezoe S, Gale K, Ishiko J, Satoh Y et al. Notch signals inhibit the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through the induction of HES1. J Biol Chem 2005; 280: 4929–4939.

    Article  CAS  Google Scholar 

  11. Sauer MG, Ericson ME, Weigel BJ, Herron MJ, Panoskaltsis-Mortari A, Kren BT et al. A novel system for simultaneous in vivo tracking and biological assessment of leukemia cells and ex vivo-generated leukemia-reactive cytotoxic T cells. Cancer Res 2004; 64: 3914–3921.

    Article  CAS  Google Scholar 

  12. Schroeder T, Just U . Notch signalling via RBP-J promotes myeloid differentiation. EMBO J 2000; 19: 2558–2568.

    Article  CAS  Google Scholar 

  13. Tan-Pertel HT, Walker L, Browning D, Miyamoto A, Weinmaster G, Gasson JC . Notch signaling enhances survival and alters differentiation of 32D myeloblasts. J Immunol 2000; 165: 4428–4436.

    Article  CAS  Google Scholar 

  14. Milner LA, Bigas A, Kopan R, Brashem-Stein C, Bernstein ID, Martin DIK . Inhibition of granulocytic differentiation by mNotch1. Proc Natl Acad Sci USA 1996; 93: 13014–13019.

    Article  CAS  Google Scholar 

  15. Stier S, Cheng T, Dombkowski D, Carlesso N, Scadden DT . Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome. Blood 2002; 99: 2369–2378.

    Article  CAS  Google Scholar 

  16. Cheng P, Nefedova Y, Miele L, Osborne BA, Gabrilovich D . Notch signaling is necessary but not sufficient for differentiation of dendritic cells. Blood 2003; 102: 3980–3988.

    Article  CAS  Google Scholar 

  17. Radtke F, Ferrero I, Wilson A, Lees R, Aguet M, MacDonald HR . Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells. J Exp Med 2000; 191: 1085–1094.

    Article  CAS  Google Scholar 

  18. Ohishi K, Varnum-Finney B, Serda RE, Anasetti C, Bernstein ID . The Notch ligand, Delta-1, inhibits the differentiation of monocytes into macrophages but permits their differentiation into dendritic cells. Blood 2001; 98: 1402–1407.

    Article  CAS  Google Scholar 

  19. Weijzen S, Velders MP, Elmishad AG, Bacon PE, Panella JR, Nickoloff BJ et al. The Notch ligand jagged-1 is able to induce maturation of monocyte-derived human dendritic cells. J Immunol 2002; 169: 4273–4278.

    Article  CAS  Google Scholar 

  20. Schroeder T, Lange C, Strehl J, Just U . Generation of functionally mature dendritic cells from the multipotential stem cell line FDCP-mix. Br J Haematol 2000; 111: 890–897.

    CAS  PubMed  Google Scholar 

  21. Rathinam C, Geffers R, Yucel R, Buer J, Welte K, Moroy T et al. The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function. Immunity 2005; 22: 717–728.

    Article  CAS  Google Scholar 

  22. Klein C, Bueler H, Mulligan RC . Comparative analysis of genetically modified dendritic cells and tumor cells as therapeutic cancer vaccines. J Exp Med 2000; 191: 1699–1708.

    Article  CAS  Google Scholar 

  23. Pear W, Aster J, Scott M, Hasserjian R, Soffer B, Sklar J et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp Med 1996; 183: 2283–2291.

    Article  CAS  Google Scholar 

  24. Pui JC, Allman D, Xu L, DeRocco S, Karnell FG, Bakkour S et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 1999; 11: 299–308.

    Article  CAS  Google Scholar 

  25. Sorrentino BP . Clinical strategies for expansion of haematopoietic stem cells. Nat Rev Immunol 2004; 4: 878–888.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Fritz-Bender-Foundation, the Elternverein für Krebskranke Kinder, the VARTA foundation, the German Ministry for Education and Research (BMBF) and the German Research Society (DFG). We thank Inga Sandrock for excellent technical support.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    C Rathinam, M Sauer, A Ghosh, A Hegazy, K Welte & C Klein

  2. Institute for Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany

    C Rudolph & B Schlegelberger

Authors
  1. C Rathinam
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  2. M Sauer
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  3. A Ghosh
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  4. C Rudolph
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  5. A Hegazy
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  6. B Schlegelberger
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  7. K Welte
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  8. C Klein
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Corresponding author

Correspondence to C Klein.

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Supplementary Information is available on the Leukemia website (http://www.nature.com/leu/)

Supplementary information

Supplementary Figure 1

Spectral karyotyping analysis of CR1 cells. (PDF 133 kb)

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Rathinam, C., Sauer, M., Ghosh, A. et al. Generation and characterization of a novel hematopoietic progenitor cell line with DC differentiation potential. Leukemia 20, 870–876 (2006). https://doi.org/10.1038/sj.leu.2404157

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  • DOI: https://doi.org/10.1038/sj.leu.2404157

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