| First Author | Ohta H | Year | 2002 |
| Journal | J Exp Med | Volume | 195 |
| Issue | 6 | Pages | 759-70 |
| PubMed ID | 11901201 | Mgi Jnum | J:75707 |
| Mgi Id | MGI:2177391 | Doi | 10.1084/jem.20011911 |
| Citation | Ohta H, et al. (2002) Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells. J Exp Med 195(6):759-70 |
| abstractText | 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. |
