QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 4 July 2006
doi: 10.1242/jcs.03038

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.03038v1 119/15/3039    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bashamboo, A. Articles by Forrester, L. M. Search for Related Content PubMed PubMed Citation Articles by Bashamboo, A. Articles by Forrester, L. M. Social Bookmarking                         What's this?

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

¹ John Hughes Bennett Laboratory, Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
² Scottish National Blood Transfusion, John Hughes Bennett Laboratory, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
³ Mouse functional Genetics, Institut Pasteur, 25 Rue du Dr Roux, 75015 Paris, France
⁴ Stem Cell and Leukaemia Proteomics Laboratory, Faculty of Medical and Human Sciences, University of Manchester, Christie Hospital, Manchester, M20 9BX, UK

^* Author for correspondence (e-mail: l.forrester{at}ed.ac.uk)

Accepted 8 May 2006

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.

Key words: KIT, Survival, ES cells, Differentiation, Apoptosis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				O. Dakhova, M. Ozen, C. J. Creighton, R. Li, G. Ayala, D. Rowley, and M. Ittmann Global Gene Expression Analysis of Reactive Stroma in Prostate Cancer Clin. Cancer Res., June 15, 2009; 15(12): 3979 - 3989. [Abstract] [Full Text] [PDF]

				J. Yu, R. Rossi, C. Hale, D. Goulding, and G. Dougan Interaction of Enteric Bacterial Pathogens with Murine Embryonic Stem Cells Infect. Immun., February 1, 2009; 77(2): 585 - 597. [Abstract] [Full Text] [PDF]