Transient induction of p53 can cause reversible quiescence and irreversible senescence. Using nutlin-3a (a small molecule that activates p53 without causing DNA damage), we have previously identified cell lines in which nutlin-3a caused quiescence. Importantly, nutlin-3a caused quiescence by actively suppressing the senescence program (while still causing cell cycle arrest). Noteworthy, in thes...

Quiescence is a fundamental concept in modelling system behaviour, as it explicitly represents the fact that no output is produced in certain states. The notion of quiescence is also essential to model-based testing: if a particular implementation under test does not provide any output, then the test evaluation algorithm must decide whether or not to allow this behaviour. To explicitly model qu...

The reversible state of proliferative arrest known as "cellular quiescence" plays an important role in tissue homeostasis and stem cell biology. By analyzing the expression of miRNAs and miRNA-processing factors during quiescence in primary human fibroblasts, we identified a group of miRNAs that are induced during quiescence despite markedly reduced expression of Exportin-5, a protein required ...

Mechanisms of tissue stem cell (SC) quiescence control are important for normal homeostasis and for preventing cancer. Cyclin-dependent kinase inhibitors (CDKis) are known inhibitors of cell cycle progression. We document CDKis expression in vivo during hair follicle stem cell (HFSC) homeostasis and find p21 (cyclin-dependent kinase inhibitor 1a, Cdkn1a), p57, and p15 up-regulated at quiescence...

OBJECTIVE Bone morphogenetic protein-9 (BMP9)/activin-like kinase-1 and delta-like 4 (DLL4)/Notch promote endothelial quiescence, and we aim to understand mechanistic interactions between the 2 pathways. We identify new targets that contribute to endothelial quiescence and test whether loss of Dll4(+/-) in adult vasculature alters BMP signaling. APPROACH AND RESULTS Human endothelial cells re...

Among the most important decisions an animal makes is whether to engage in active movement and feeding behavior or to become quiescent. The molecular signaling mechanisms underlying this decision remain largely unknown. The nematode Caenorhabditis elegans displays sleep-like quiescence following exposures that result in cellular stress. The neurosecretory ALA neuron is required for this stress-...

Throughout life, neural stem cells (NSCs) in the adult hippocampus persistently generate new neurons that modify the neural circuitry. Adult NSCs constitute a relatively quiescent cell population but can be activated by extrinsic neurogenic stimuli. However, the molecular mechanism that controls such reversible quiescence and its physiological significance have remained unknown. Here, we show t...

Cellular senescence is a form of irreversible growth arrest historically associated with the exhaustion of replicative potential of in vitro cultured cells. Senescence can be triggered by many stimuli, including telomere attrition, DNA damage, oxidative stress, activation of oncogenes, and inactivation of tumor suppressor genes, and plays important roles in tumor suppression, organism aging, ti...

This paper presents an analytical study of the phenomenon of recurrent infection, that is, transient episodes of high viral reproduction, separated by long periods of relative quiescence, which are observed in many persistent infections; the “viral blips” observed during chronic infection with human immunodeficiency virus (HIV) are a well-known example. Although in-host models which incorporate...

The tuberous sclerosis complex (TSC)-mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cycling, with increased mitochondrial biogenesis and ele...