A new description of cellular quiescence.
A new description of cellular quiescence.
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DOI：
10.1371/journal.pbio.0040083
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发表时间：
2006-03
期刊：
影响因子：
9.8
通讯作者：
Roberts JM
中科院分区：
文献类型：
--
作者：
Coller HA;Sang L;Roberts JM
细胞静止，定义为可逆的生长/增殖停滞，被认为代表由不同的抗有丝分裂信号诱导的同质状态。我们使用转录谱来表征人类二倍体成纤维细胞暴露于三个独立的信号-有丝分裂原撤退，接触抑制和粘附损失后退出细胞周期。我们在这里表明，每个信号引起一组独特的基因的调节，已知这些基因对停止生长和分裂很重要。因此，与预期相反，细胞进入由起始信号决定的不同静止状态。然而，在这种多样性的基础上，我们发现了一组基因，它们在非分裂细胞中的特异性表达是信号无关的，因此代表了静止本身，而不是诱导它的信号。这种成纤维细胞“静止程序”包含强制非分裂状态的基因，并确保了细胞周期停滞的可逆性。我们进一步证明，一种机制，其中的可逆性的静止是保险的终端分化的抑制。静止程序的表达并不简单地是退出细胞周期的下游结果，因为关键部分，包括那些参与抑制分化的部分，在直接抑制细胞周期蛋白依赖性激酶引起的细胞周期停滞期间没有重现。这些研究为理解细胞静止的正常生物学奠定了基础。由不同信号诱导退出细胞周期的成纤维细胞的转录谱揭示了细胞静止途径的区别和共性。
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. Transcriptional profiling of fibroblasts induced to exit the cell cycle by distinct signals reveals distinctions and commonalities in the pathways to cellular quiescence.
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