PMID- 11532354
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20191025
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 29
IP  - 9
DP  - 2001 Sep
TI  - HOXB4 overexpression mediates very rapid stem cell regeneration and competitive 
      hematopoietic repopulation.
PG  - 1125-34
AB  - OBJECTIVE: Hox transcription factors have emerged as important regulators of 
      hematopoiesis. In particular, we have shown that overexpression of HOXB4 in mouse 
      bone marrow can greatly enhance the level of hematopoietic stem cell (HSC) 
      regeneration achieved at late times (> 4 months) posttransplantation. The 
      objective of this study was to resolve if HOXB4 increases the rate and/or 
      duration of HSC regeneration, and also to see if this enhancement was associated 
      with impaired production of end cells or would lead to competitive reconstitution 
      of all compartments. METHODS: Retroviral vectors were generated with the GFP 
      reporter gene +/- HOXB4 to enable the isolation and direct tracking of transduced 
      cells in culture or following transplantation. Stem cell recovery was measured by 
      limit dilution assay for long-term competitive repopulating cells (CRU). RESULTS: 
      HOXB4-overexpressing cells have enhanced growth in vitro, as demonstrated by 
      their rapid dominance in mixed cultures and their shortened population doubling 
      time. Furthermore, HOXB4-transduced cells have a marked competitive repopulating 
      advantage in vivo in both primitive and mature compartments. CRU recovery in 
      HOXB4 recipients was extremely rapid, reaching 25% of normal by 14 days 
      posttransplant or some 80-fold greater than control transplant recipients, and 
      attaining normal numbers by 12 weeks. Mice transplanted with even higher numbers 
      of HOXB4-transduced CRU regenerated up to but not beyond the normal CRU levels. 
      CONCLUSIONS: HOXB4 is a potent enhancer of primitive hematopoietic cell growth, 
      likely by increasing self-renewal probability but without impairing homeostatic 
      control of HSC population size or the rate of production and maintenance of 
      mature end cells.
FAU - Antonchuk, J
AU  - Antonchuk J
AD  - Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
FAU - Sauvageau, G
AU  - Sauvageau G
FAU - Humphries, R K
AU  - Humphries RK
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxb4 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Hematopoiesis/*drug effects
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/cytology/*physiology
MH  - Homeodomain Proteins/genetics/metabolism/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Regeneration/*drug effects
MH  - Transcription Factors/genetics/metabolism/*pharmacology
MH  - Transduction, Genetic
EDAT- 2001/09/05 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/09/05 10:00
PHST- 2001/09/05 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/09/05 10:00 [entrez]
AID - S0301-472X(01)00681-6 [pii]
AID - 10.1016/s0301-472x(01)00681-6 [doi]
PST - ppublish
SO  - Exp Hematol. 2001 Sep;29(9):1125-34. doi: 10.1016/s0301-472x(01)00681-6.