Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors

Authors

  • Elaine Spooncer,

    Corresponding author
    1. Department of Experimental Haematology, Paterson Laboratories, Christie Hospital and Holt Radium Institute, Withington, Manchester M20 9BX, United Kingdom
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  • Clare M. Heyworth,

    1. Department of Experimental Haematology, Paterson Laboratories, Christie Hospital and Holt Radium Institute, Withington, Manchester M20 9BX, United Kingdom
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  • A. Dunn,

    1. Ludwig Institute for Cancer Research, Melbourne, Australia
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  • T. Michael Dexter

    1. Department of Experimental Haematology, Paterson Laboratories, Christie Hospital and Holt Radium Institute, Withington, Manchester M20 9BX, United Kingdom
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*To whom offprint requests should be sent

Abstract

Abstract. Interleukin-3 (IL-3)-dependent cell lines (FDCP-mix) were cloned and isolated from long-term bone-marrow cultures infected with src-MoMuLV. These cell lines have many of the characteristics of hematopoietic stem cells. Early isolates of the FDCP-mix cells form spleen colonies in irradiated mice and establish long-term hematopoiesis on irradiated marrow stroma in vitro in the absence of IL-3. These two properties of the cells are lost within 15 weeks of establishing the cell lines, but the cell lines retain their ability to differentiate in a multilineage response to hematopoietic growth factors and to hematopoietic stromal cells, as well as to self-renew in the presence of IL-3. The choice between differentiation and self-renewal in FDCP-mix cells can clearly be modified by culture conditions: in particular, cultures containing horse serum preferentially promote self-renewal, whereas cultures containing fetal calf serum preferentially promote differentiation. The FDCP-mix cell lines are not leukemic, nor do they contain the src oncogene. Their ability to respond to hematopoietic growth factors and stroma in a similar manner to normal hematopoietic cells makes them a valuable model for studying the regulation of hemopoietic cell self-renewal and differentiation.

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