Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells.
The rae28 gene (rae28), also designated as mph1, is a mammalian ortholog of the Drosophila polyhomeotic gene, a member of Polycomb group genes (PcG). rae28 constitutes PcG complex 1 for maintaining transcriptional states which have been once initiated, presumably through modulation of the chromatin structure. Hematopoietic activity was impaired in the fetal liver of rae28-deficient animals (rae28-/-), as demonstrated by progressive reduction of hematopoietic progenitors of multilineages and poor expansion of colony forming units in spleen (CFU-S(12)) during embryonic development. An in vitro long-term culture-initiating cell assay suggested a reduction in hematopoietic stem cells (HSCs), which was confirmed in vivo by reconstitution experiments in lethally irradiated congenic recipient mice. The competitive repopulating units (CRUs) reflect HSCs supporting multilineage blood-cell production. CRUs were generated, whereas the number of CRUs was reduced by a factor of 20 in the rae28-/- fetal liver. We also performed serial transplantation experiments to semiquantitatively measure self-renewal activity of CRUs in vivo. Self-renewal activity of CRUs was 15-fold decreased in rae28-/-. Thus the compromised HSCs were presumed to reduce hematopoietic activity in the rae28-/- fetal liver. This is the first report to suggest that rae28 has a crucial role in sustaining the activity of HSCs to maintain hematopoiesis.
Ohta
Hideaki
H
Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi-1, Higashinari, Osaka 537-8511, Japan.
Sawada
Akihisa
A
Kim
Ji Yoo
JY
Tokimasa
Sadao
S
Nishiguchi
Seiji
S
Humphries
R Keith
RK
Hara
Junichi
J
Takihara
Yoshihiro
Y
D000818:Animals; D002352:Carrier Proteins; D003114:Colony-Forming Units Assay; D005786:Gene Expression Regulation / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063150:Polycomb Repressive Complex 1
D002352:Carrier Proteins; D018398:Homeodomain Proteins; C103827:Phc1 protein, mouse; D063150:Polycomb Repressive Complex 1