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

2.50
Hdl Handle:
http://hdl.handle.net/10541/72689
Title:
The survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway.
Authors:
Bashamboo, Anu; Taylor, A Helen; Samuel, Kay; Panthier, Jean-Jacque; Whetton, Anthony D; Forrester, Lesley M
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.
Affiliation:
John Hughes Bennett Laboratory, Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
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
Issue Date:
1-Aug-2006
URI:
http://hdl.handle.net/10541/72689
DOI:
10.1242/jcs.03038
PubMed ID:
16820414
Type:
Article
Language:
en
ISSN:
0021-9533
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBashamboo, Anu-
dc.contributor.authorTaylor, A Helen-
dc.contributor.authorSamuel, Kay-
dc.contributor.authorPanthier, Jean-Jacque-
dc.contributor.authorWhetton, Anthony D-
dc.contributor.authorForrester, Lesley M-
dc.date.accessioned2009-07-07T10:55:43Z-
dc.date.available2009-07-07T10:55:43Z-
dc.date.issued2006-08-01-
dc.identifier.citationThe survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway. 2006, 119 (Pt 15):3039-46 J. Cell. Sci.en
dc.identifier.issn0021-9533-
dc.identifier.pmid16820414-
dc.identifier.doi10.1242/jcs.03038-
dc.identifier.urihttp://hdl.handle.net/10541/72689-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Survival-
dc.subject.meshEmbryonic Stem Cells-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshMutation-
dc.subject.meshPhenotype-
dc.subject.meshProto-Oncogene Proteins c-kit-
dc.subject.meshSignal Transduction-
dc.subject.meshStem Cell Factor-
dc.subject.meshTacrolimus-
dc.titleThe survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway.en
dc.typeArticleen
dc.contributor.departmentJohn Hughes Bennett Laboratory, Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.en
dc.identifier.journalJournal of Cell Scienceen

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