Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells.
Identification of the molecular mechanisms that can promote human hematopoietic stem cell amplification is a major goal in experimental and clinical hematology. Recent data indicate that a variety of regulatory molecules active in early development may also play a role in the maintenance of hematopoietic stem cells with repopulating activity. One important class of early developmental genes determining hematopoietic development are homeobox transcription factors. Here, we report that retrovirally mediated expression of the homeobox gene HOXB4 rapidly triggers an increase in the number of human hematopoietic cord blood cells with stem cell and progenitor cell properties detected both by in vitro and in vivo assays. This growth enhancement extended across primitive myeloid-erythroid and B-lymphoid progenitors but did not lead to alterations in the balance of lymphomyeloid reconstitution in vivo, suggesting that HOXB4 does not affect control of end-cell output. These findings reveal HOXB4 as a novel, positive regulator of the primitive growth activity of human hematopoietic progenitor cells and underline the relevance of early developmental factors for stem cell fate decisions.
Terry Fox Laboratory, British Columbia Cancer Agency, and the Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Christian
C
Buske
Michaela
M
Feuring-Buske
Carolina
C
Abramovich
Karsten
K
Spiekermann
Connie J
CJ
Eaves
Laure
L
Coulombel
Guy
G
Sauvageau
Donna E
DE
Hogge
R Keith
RK
Humphries
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005312:Fetal Blood; D006410:Hematopoiesis / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014161:Transduction, Genetic / Q000379:methods
C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D014157:Transcription Factors