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First published online June 17, 2009
In this issue |
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Defining the underlying pathways that control self-renewal and proliferation is an important goal in embryonic stem cell (ESC) research. On the basis of previous work showing that phosphoinositide 3-kinase (PI3K) family members are involved in regulating the behaviour of ESCs, Emmajayne Kingham and Melanie Welham (p. 2311) now seek to understand the role of specific class-IA PI3K isoforms in mouse ESC self-renewal and proliferation. Each of the three class-IA PI3Ks comprises a 110-kDa catalytic subunit (p110
, p110β or p110
) and a regulatory subunit; differential roles of these three catalytic isoforms have been reported in many cellular processes. In this study, the authors specifically inhibit these three different p110 isoforms using isoform-selective small-molecule inhibitors or small interfering RNAs to investigate their respective roles in regulating ESC behaviour. They find that p110β, but not p110 or p110, is required to maintain optimal ESC self-renewal. By contrast, p110 regulates ESC proliferation. The authors conclude that different isoforms of the class-IA PI3K catalytic subunit are coupled to self-renewal and proliferation in mouse ESCs. However, because there is also evidence for crosstalk between the different isoforms, they hypothesise that PI3K signalling might link self-renewal with proliferation in ESCs.
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