title: Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells.
abstract: 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.
authors.affiliation: Department of Developmental Biology and Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi-1, Higashinari, Osaka 537-8511, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohta
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.forename: Ji Yoo
authors.initials: JY
authors.lastname: Kim
authors.forename: Sadao
authors.initials: S
authors.lastname: Tokimasa
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takihara
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D018398:Homeodomain Proteins; C103827:Phc1 protein, mouse; D063150:Polycomb Repressive Complex 1