The survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway.
Authors
Bashamboo, AnuTaylor, 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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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 ScienceDOI
10.1242/jcs.03038PubMed ID
16820414Type
ArticleLanguage
enISSN
0021-9533ae974a485f413a2113503eed53cd6c53
10.1242/jcs.03038
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