A Functional Screen to Identify Novel Effectors of Hematopoietic Stem Cell Activity

Eric Deneault, Sonia Cellot, Amelie Faubert, Jean-Philippe Laverdure, Melanie Frechette, Jalila Chagraoul, Nadine Mayotte, Martin Sauvageau, Stephen Bek Ngie Ting, Guy Sauvageau

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    96 Citations (Scopus)

    Abstract

    Despite tremendous progress made toward the identification of the molecular circuitry that governs cell fate in embryonic stem cells, genes controlling this process in the adult hematopoietic stem cell have proven to be more difficult to unmask. We now report the results of a novel gain-of-function screening approach, which identified a series of 18 nuclear factors that affect hematopoietic stem cell activity. Overexpression of ten of these factors resulted in an increased repopulating activity compared to unmanipulated cells. Interestingly, at least four of the 18 factors, Fos, Tcfec, Hmgb1, and Sfpi1, show non-cell-autonomous functions. The utilization of this screening method together with the creation of a database enriched for potential determinants of hematopoietic stem cell self-renewal will serve as a resource to uncover regulatory networks in these cells. A? 2009 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)369 - 379
    Number of pages11
    JournalCell
    Volume137
    Issue number2
    DOIs
    Publication statusPublished - 2009

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