PMID- 15183898
OWN - NLM
STAT- MEDLINE
DCOM- 20040811
LR  - 20211203
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 32
IP  - 6
DP  - 2004 Jun
TI  - Polycomb group gene mel-18 modulates the self-renewal activity and cell cycle 
      status of hematopoietic stem cells.
PG  - 571-8
AB  - OBJECTIVE: Mel-18 is a member of the mammalian Polycomb group (PcG) genes. This 
      family of genes regulates global gene expression in many biologic processes, 
      including hematopoiesis and anterior-posterior axis formation by manipulating 
      specific target genes, including members of the Hox family. Here, we demonstrate 
      that mel-18 negatively regulates the self-renewal activity of hematopoietic stem 
      cells (HSCs). MATERIALS AND METHODS: Long-term reconstitution activity was 
      evaluated by competitive repopulating unit (CRU) and mean activity of the stem 
      cells (MAS) assays in vivo in bone marrow cells (BMCs) derived from mel-18(-/-) 
      and mel-18 tg mice. The expression levels of mel-18 and Hoxb4 were measured by 
      quantitative real-time reverse transcription polymerase chain reaction. RESULTS: 
      The Hoxb4 gene was highly expressed in HSCs derived from mel-18(-/-) mice. The 
      observed CRUs were 3.21, 4.77, 3.32, and 1.64 CRU per 10(5) BMCs in mel-18(+/+), 
      mel-18(-/-), C57BL/6, and mel-18 tg, respectively. MAS was 0.58, 0.18, 0.41, and 
      5.89 in mel-18(+/+), mel-18(-/-), C57BL/6, and mel-18 tg, respectively. The 
      percentage in G0 phase HSCs (lin(-)flk2(-)c-Kit(+)Sca1+ cells) was increased in 
      mel-18(-/-) mice and decreased in mel-18 tg mice. CONCLUSION: Loss or knockdown 
      of mel-18 leads to the expression of Hoxb4, an increase in the proportion of HSCs 
      in G0 phase, and the subsequent promotion of HSC self-renewal. These findings 
      will enable us to develop new approaches for controlling HSC activity for 
      hematopoietic transplantations based on ex vivo expansion of HSCs.
FAU - Kajiume, Teruyuki
AU  - Kajiume T
AD  - Department of Immunology, Graduate School of Biomedical Science, Hiroshima 
      University, Hiroshima, Japan.
FAU - Ninomiya, Yuichi
AU  - Ninomiya Y
FAU - Ishihara, Hiroto
AU  - Ishihara H
FAU - Kanno, Rieko
AU  - Kanno R
FAU - Kanno, Masamoto
AU  - Kanno M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxb4 protein, mouse)
RN  - 0 (Pcgf6 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
RN  - W659G165T1 (Pyronine)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Transplantation/*physiology
MH  - Cell Cycle/*physiology
MH  - DNA Primers
MH  - DNA-Binding Proteins/deficiency/*genetics
MH  - Genes, Homeobox
MH  - Hematopoietic Stem Cells/cytology/*physiology
MH  - Homeodomain Proteins/genetics
MH  - Immunosuppression Therapy/methods
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multigene Family
MH  - Polycomb Repressive Complex 1
MH  - Pyronine/analysis
MH  - Resting Phase, Cell Cycle
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors
MH  - Transplantation, Homologous
MH  - Whole-Body Irradiation
MH  - Zinc Fingers/genetics
EDAT- 2004/06/09 05:00
MHDA- 2004/08/12 05:00
CRDT- 2004/06/09 05:00
PHST- 2003/09/26 00:00 [received]
PHST- 2004/03/05 00:00 [revised]
PHST- 2004/03/09 00:00 [accepted]
PHST- 2004/06/09 05:00 [pubmed]
PHST- 2004/08/12 05:00 [medline]
PHST- 2004/06/09 05:00 [entrez]
AID - S0301472X04000876 [pii]
AID - 10.1016/j.exphem.2004.03.001 [doi]
PST - ppublish
SO  - Exp Hematol. 2004 Jun;32(6):571-8. doi: 10.1016/j.exphem.2004.03.001.