Reciprocal expression of Bmi1 and Mel-18 is associated with functioning of primitive hematopoietic cells.
OBJECTIVE
The Polycomb-group (PcG) genes regulate global gene expression in many biological processes, including hematopoiesis, by manipulating specific target genes. It is known that various PcG genes regulate self-renewal of hematopoietic stem cells (HSCs). Here we have shown that the reciprocal expression of PcG proteins regulates self-renewal and differentiation of HSCs.


METHODS
We used murine and human bone marrow cells and evaluated the reciprocal expression of PcG proteins on the basis of their respective intranuclear distributions. PcG-gene expression in HSCs was knocked down by small interfering RNAs. The function of each gene in HSCs was analyzed in vitro and in vivo.


RESULTS
Cells were either Bmi1-positive or Mel-18-positive. The Bmi1-positive cells contained very little amounts of Mel-18 and vice versa. The bmi1-knockdown marrow cells did not show HSC function, while the mel-18-knockdown marrow cells showed increased stem cell function. Results of the analysis on human cells were similar to those observed in case of murine cells. In a clinical investigation, transplantation using sources with a low Bmi1 to Mel-18 ratio was associated with early hematopoietic recovery.


CONCLUSIONS
Reciprocal expression of Bmi1 and Mel-18 regulated HSC function. Here, we observed that expression of the PcG genes-bmi1 and mel-18-is correlated with self-renewal and differentiation of HSCs. Thus, it was suggested that the balance between Bmi1 and Mel-18 regulates self-renewal of HSCs.
Kajiume
Teruyuki
T
Department of Pediatrics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. kajiume@hiroshima-u.ac.jp
Ohno
Norioki
N
Sera
Yasuhiko
Y
Kawahara
Yumi
Y
Yuge
Louis
L
Kobayashi
Masao
M
D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C489421:Bmi1 protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C066476:Pcgf6 protein, mouse; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1