Cancer Institute A national cancer institute
designated cancer center

Atul Butte

Publication Details

  • Hematopoietic Stem Cell Quiescence Is Maintained by Compound Contributions of the Retinoblastoma Gene Family CELL STEM CELL Viatour, P., Somervaille, T. C., Venkatasubrahmanyam, S., Kogan, S., McLaughlin, M. E., Weissman, I. L., Butte, A. J., Passegue, E., Sage, J. 2008; 3 (4): 416-428

    Abstract:

    Individual members of the retinoblastoma (Rb) tumor suppressor gene family serve critical roles in the control of cellular proliferation and differentiation, but the extent of their contributions is masked by redundant and compensatory mechanisms. Here we employed a conditional knockout strategy to simultaneously inactivate all three members, Rb, p107, and p130, in adult hematopoietic stem cells (HSCs). Rb family triple knockout (TKO) mice develop a cell-intrinsic myeloproliferation that originates from hyperproliferative early hematopoietic progenitors and is accompanied by increased apoptosis in lymphoid progenitor populations. Loss of quiescence in the TKO HSC pool is associated with an expansion of these mutant stem cells but also with an enhanced mobilization and an impaired reconstitution potential upon transplantation. The presence of a single p107 allele is sufficient to largely rescue these defects. Thus, Rb family members collectively maintain HSC quiescence and the balance between lymphoid and myeloid cell fates in the hematopoietic system.

    View details for DOI 10.1016/j.stem.2008.07.009

    View details for Web of Science ID 000260149800012

    View details for PubMedID 18940733

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