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Publication : Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1.

First Author  Iwama A Year  2004
Journal  Immunity Volume  21
Issue  6 Pages  843-51
PubMed ID  15589172 Mgi Jnum  J:94683
Mgi Id  MGI:3513696 Doi  10.1016/j.immuni.2004.11.004
Citation  Iwama A, et al. (2004) Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity 21(6):843-51
abstractText  The Polycomb group (PcG) gene Bmi-1 has recently been implicated in the maintenance of hematopoietic stem cells (HSC) from loss-of-function analysis. Here, we demonstrate that increased expression of Bmi-1 promotes HSC self-renewal. Forced expression of Bmi-1 enhanced symmetrical cell division of HSCs and mediated a higher probability of inheritance of stemness through cell division. Correspondingly, forced expression of Bmi-1, but not the other PcG genes, led to a striking ex vivo expansion of multipotential progenitors and marked augmentation of HSC repopulating capacity in vivo. Loss-of-function analyses revealed that among PcG genes, absence of Bmi-1 is preferentially linked with a profound defect in HSC self-renewal. Our findings define Bmi-1 as a central player in HSC self-renewal and demonstrate that Bmi-1 is a target for therapeutic manipulation of HSCs.
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