In vitro and in vivo expansion of hematopoietic stem cells.
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.
Sauvageau
Guy
G
Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Institute of Research in Immunology and Cancer, University of Montreal, CP 6128, Downtown Station, Quebec, Canada H3C 3J7. guy.sauvageau@umontreal.ca
Iscove
Norman N
NN
Humphries
R Keith
RK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
D018076:DNA, Complementary; D016298:Hematopoietic Cell Growth Factors; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors