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    The survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway.

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    Authors
    Bashamboo, Anu
    Taylor, A Helen
    Samuel, Kay
    Panthier, Jean-Jacque
    Whetton, Anthony D
    Forrester, Lesley M
    Affiliation
    John Hughes Bennett Laboratory, Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
    Issue Date
    2006-08-01
    
    Metadata
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    Abstract
    The stem cell factor (SCF)-KIT signal transduction pathway plays a role in the proliferation, differentiation and survival of a range of stem and progenitor cell types but little is known about its function in embryonic stem (ES) cells. We generated ES cells carrying a null allele of Kit as well as a knock-in allele that encodes an SCF-independent hybrid KIT receptor that can be activated by the FKBP binding drug, AP20187. KIT null ES cells die when induced to differentiate upon withdrawal of leukaemia inhibitory factor in monolayer culture. This phenotype is recapitulated in wild-type ES cells treated with a KIT-neutralising antibody and reversed in mutant cells by activation of the hybrid KIT receptor. Differentiating KIT null ES cells exhibit elevated levels of DNA laddering and reduced BCL2 expression, indicative of apoptosis. We conclude that mouse ES cell differentiation in vitro is dependent on the SCF-KIT pathway contrasting with the apparently normal differentiation of KIT null inner cell mass or epiblast cells in vivo. This discrepancy could be explained by the presence of compensatory signals in the embryo or it could lend support to the idea of a phenotypic relationship between ES cells and early germ cells.
    Citation
    The survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway. 2006, 119 (Pt 15):3039-46 J. Cell. Sci.
    Journal
    Journal of Cell Science
    URI
    http://hdl.handle.net/10541/72689
    DOI
    10.1242/jcs.03038
    PubMed ID
    16820414
    Type
    Article
    Language
    en
    ISSN
    0021-9533
    ae974a485f413a2113503eed53cd6c53
    10.1242/jcs.03038
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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