a new description of cellular quiescence一个新的细胞静止的描述.pdfVIP

PLoS BIOLOGY A New Description of Cellular Quiescence Hilary A. Coller1[¤*, Liyun Sang1,2[, James M. Roberts1,3 1 Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 2 Molecular Cellular Biology Program, University of Washington, Seattle, Washington, United States of America, 3 Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America 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,