1. ¹Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Institute of Research in Immunology and Cancer, University of Montreal, CP 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7
2. ²Department of Medicine, University of Montreal, Canada
3. ³Division of Hematology, Hospital Maisonneuve-Rosemont, Canada
4. ⁴Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, Ontario, Canada
5. ⁵Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3
6. ⁶Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4E3

Correspondence: G Sauvageau, IRIC – Institute of Research in Immunology and Cancer, University of Montreal, CP 6128, Downtown Station, Montreal, Quebec, Canada H3C 3J7. E-mail: guy.sauvageau@umontreal.ca; RK Humphries, Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3. E-mail: khumphri@bccrc.ca

Abstract

The capacity for sustained self-renewal – the generation of daughter cells having the same regenerative properties as the parent cell – is the defining feature of hematopoietic stem cells (HSCs). Strong evidence exists that self-renewal of HSC is under extrinsic biological control in vivo. A variety of cytokines, morphogenic ligands and associated signaling components influence self-renewal in culture and in vivo. Specific homeobox transcription factors act as powerful intrinsic agonists of HSC self-renewal in vitro and in vivo when supplied either as transduced cDNAs or as externally delivered proteins. These findings provide tools for deepening our knowledge of mechanism and for achievement of clinically useful levels of HSC expansion.