A new description of cellular quiescence

被引:380
作者
Coller, HA
Sang, LY
Roberts, JM
机构
[1] Fred Hutchinson Canc Res Ctr, Dept Basic Sci, Seattle, WA 98104 USA
[2] Univ Washington, Cell & Mol Biol Program, Seattle, WA 98195 USA
[3] Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98104 USA
关键词
D O I
10.1371/journal.pbio.0040083
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cellular quiescence, defined as reversible growth/proliferation arrest, is thought to represent a homogenous state induced by diverse anti-mitogenic signals. We used transcriptional profiling to characterize human diploid fibroblasts that exited the cell cycle after exposure to three independent signals-mitogen withdrawal, contact inhibition, and loss of adhesion. We show here that each signal caused regulation of a unique set of genes known to be important for cessation of growth and division. Therefore, contrary to expectation, cells enter different quiescent states that are determined by the initiating signal. However, underlying this diversity we discovered a set of genes whose specific expression in non-dividing cells was signal-independent, and therefore representative of quiescence per se, rather than the signal that induced it. This fibroblast "quiescence program'' contained genes that enforced the non-dividing state, and ensured the reversibility of the cell cycle arrest. We further demonstrate that one mechanism by which the reversibility of quiescence is insured is the suppression of terminal differentiation. Expression of the quiescence program was not simply a downstream consequence of exit from the cell cycle, because key parts, including those involved in suppressing differentiation, were not recapitulated during the cell cycle arrest caused by direct inhibition of cyclin-dependent kinases. These studies form a basis for understanding the normal biology of cellular quiescence.
引用
收藏
页码:329 / 349
页数:21
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