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Polycomb Group Gene rae28 Is Required for Sustaining Activity of Hematopoietic Stem Cells
Open accessAbstract
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-S12) 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.
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Self-citationvan der Vlag, J., & Otte, A. P. (1999) · Nature Genetics · doi:10.1038/70602 · Cited by 527
Functions of mammalian Polycomb group and trithorax group related genes.
Gould, A. (1997) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(97)80075-5 · Cited by 198
Cited by
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003) · Nature · doi:10.1038/nature01587 · Cited by 1,871
A Stem Cell Molecular Signature
Ivanova, N. B., Dimos, J. T., Schaniel, C., Hackney, J. A., Moore, K. A., & Lemischka, I. R. (2002) · Science · doi:10.1126/science.1073823 · Cited by 1,542
Valk-Lingbeek, M. E., Bruggeman, S. W. M., & van Lohuizen, M. (2004) · Cell · doi:10.1016/j.cell.2004.08.005 · Cited by 743
Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
Iwama, A., Oguro, H., Negishi, M., Kato, Y., Morita, Y., Tsukui, H., Ema, H., Kamijo, T., Katoh-Fukui, Y., Koseki, H., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.11.004 · Cited by 515
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Metadata
- Authors
- Ohta, H., Sawada, A., Kim, J. Y., Tokimasa, S., Nishiguchi, S., Humphries, R. K., Hara, J., & Takihara, Y.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-03-18
- Volume
- 195
- Issue
- 6
- Pages
- 759-770
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2158337417
- Cited by
- 182
- References
- 4
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- green
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- Ohta, H., Sawada, A., Kim, J. Y., Tokimasa, S., Nishiguchi, S., Humphries, R. K., Hara, J., & Takihara, Y. (2002). Polycomb Group Gene rae28 Is Required for Sustaining Activity of Hematopoietic Stem Cells. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20011911
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