Re: Stem Cell 'Master Gene' Found

From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Fri May 30 2003 - 12:16:58 MDT

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    On Fri, 30 May 2003, Brett Paatsch wrote:

    > Extropes, meet the Nanog gene (and protein) named after the
    > mythic Celtic land of the ever-young, Tir nan Og.

    Here is the abstract for this (it doesn't seem to be in PubMed
    yet but Cell has the information).

    Robert

    > Copyyright ©2003 Cell Press.
    > Cell, Vol 113, 643-655, 30 May 2003
    >
    > Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor
    > in Embryonic Stem Cells Ian Chambers, Douglas Colby, Morag Robertson,
    > Jennifer Nichols, Sonia Lee, Susan Tweedie, and Austin Smith
    >
    > Institute for Stem Cell Research, University of Edinburgh, King's
    > Buildings, West Mains Road, Edinburgh EH9 3JQ, Scotland, United Kingdom
    >
    >
    > Embryonic stem (ES) cells undergo extended proliferation while remaining
    > poised for multilineage differentiation. A unique network of
    > transcription factors may characterize self-renewal and simultaneously
    > suppress differentiation. We applied expression cloning in mouse ES
    > cells to isolate a self-renewal determinant. Nanog is a divergent
    > homeodomain protein that directs propagation of undifferentiated ES
    > cells. Nanog mRNA is present in pluripotent mouse and human cell lines,
    > and absent from differentiated cells. In preimplantation embryos, Nanog
    > is restricted to founder cells from which ES cells can be derived.
    > Endogenous Nanog acts in parallel with cytokine stimulation of Stat3 to
    > drive ES cell self-renewal. Elevated Nanog expression from transgene
    > constructs is sufficient for clonal expansion of ES cells, bypassing
    > Stat3 and maintaining Oct4 levels. Cytokine dependence, multilineage
    > differentiation, and embryo colonization capacity are fully restored
    > upon transgene excision. These findings establish a central role for
    > Nanog in the transcription factor hierarchy that defines ES cell
    > identity.
    >



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