Staying alive

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 05/2012; 11(9):1680-96. DOI: 10.4161/cc.19879
Source: PubMed


Quiescence is a state of reversible cell cycle arrest that can grant protection against many environmental insults. In some systems, cellular quiescence is associated with a low metabolic state characterized by a decrease in glucose uptake and glycolysis, reduced translation rates and activation of autophagy as a means to provide nutrients for survival. For cells in multiple different quiescence model systems, including Saccharomyces cerevisiae, mammalian lymphocytes and hematopoietic stem cells, the PI3Kinase/TOR signaling pathway helps to integrate information about nutrient availability with cell growth rates. Quiescence signals often inactivate the TOR kinase, resulting in reduced cell growth and biosynthesis. However, quiescence is not always associated with reduced metabolism; it is also possible to achieve a state of cellular quiescence in which glucose uptake, glycolysis and flux through central carbon metabolism are not reduced. In this review, we compare and contrast the metabolic changes that occur with quiescence in different model systems.

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    • "Because of this, a proportion of these cells exist in a non-proliferative state (quiescence) for prolonged periods, thereby preserving the adult stem cell pool by preventing proliferative stress and precocious commitment to differentiation (Valcourt et al., 2012; Cheung and Rando, 2013). "
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    ABSTRACT: Nuclear factor one (NFI) transcription factors are a group of site-specific DNA-binding proteins that are emerging as critical regulators of stem cell biology. During development NFIs promote the production of differentiated progeny at the expense of stem cell fate, with Nfi null mice exhibiting defects such as severely delayed brain and lung maturation, skeletomuscular defects and renal abnormalities, phenotypes that are often consistent with patients with congenital Nfi mutations. Intriguingly, recent research suggests that in adult tissues NFI factors play a qualitatively different role than during development, with NFIs serving to promote the survival and maintenance of slow-cycling adult stem cell populations rather than their differentiation. Here we review the role of NFI factors in development, largely focusing on their role as promoters of stem cell differentiation, and attempt to reconcile this with the emerging role of NFIs in adult stem cell niches. Developmental Dynamics, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Mar 2015 · Developmental Dynamics
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    • "showed that down-regulated mRNAs were mostly involved in the cell cycle (e.g., GO terms: ''cell cycle'' and ''chromosome'') and DNA and RNA metabolism (''DNA metabolic process'' and ''RNA processing''), as expected for a cell cyclearrested cell population (Fig. 1K). Other down-regulated genes were associated with protein translation (''ribonucleotide complex'' and ''ribosome biogenesis''), which is reminiscent of the reduction in protein synthesis associated with quiescence in many mammalian cells as well as yeast and bacteria (Valcourt et al. 2012). Conversely, up-regulated genes included the cyclindependent kinase inhibitor Cdkn2b/p15/INK4B (fold change = 17.5; "
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    ABSTRACT: The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, the transcriptional mechanisms involved are mostly unknown, largely due to lack of a cell culture model. In this study, we first demonstrate that NSC cultures (NS cells) exposed to BMP4 acquire cellular and transcriptional characteristics of quiescent cells. We then use epigenomic profiling to identify enhancers associated with the quiescent NS cell state. Motif enrichment analysis of these enhancers predicts a major role for the nuclear factor one (NFI) family in the gene regulatory network controlling NS cell quiescence. Interestingly, we found that the family member NFIX is robustly induced when NS cells enter quiescence. Using genome-wide location analysis and overexpression and silencing experiments, we demonstrate that NFIX has a major role in the induction of quiescence in cultured NSCs. Transcript profiling of NS cells overexpressing or silenced for Nfix and the phenotypic analysis of the hippocampus of Nfix mutant mice suggest that NFIX controls the quiescent state by regulating the interactions of NSCs with their microenvironment.
    Full-text · Article · Aug 2013 · Genes & development
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    • "While the nominal metabolic capacity of the quiescent cell likely allows a subset of DNA repair mechanisms to operate continuously, the relative activity of different systems in growing and nongrowing states remains uncertain, and distinct organisms favor different strategies. Some microorganisms arrest growth with a single chromosome (Valcourt et al., 2012), while others, such as M. tuberculosis, exit the cell cycle with two chromosomal copies (Wayne, 1977). Thus, high-fidelity recombinational repair mechanisms, which often dominate in growing cells, are only available to a subset of quiescent organisms. "
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    ABSTRACT: All microorganisms are exposed to periodic stresses that inhibit growth. Many bacteria and fungi weather these periods by entering a hardy, nonreplicating state, often termed quiescence or dormancy. When this occurs during an infection, the resulting slowly growing pathogen is able to tolerate both immune insults and prolonged antibiotic exposure. While the stresses encountered in a free-living environment may differ from those imposed by host immunity, these growth-limiting conditions impose common pressures, and many of the corresponding microbial responses appear to be universal. In this review, we discuss the common features of these growth-limited states, which suggest new approaches for treating chronic infections such as tuberculosis.
    Full-text · Article · Jun 2013 · Cell host & microbe
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