Modelling mammalian cellular quiescence

Abstract

One contribution of 10 to a Theme Issue 'Computational cell biology: from the past to the future'. Cellular quiescence is a reversible non-proliferating state. The reactivation of 'sleep-like' quiescent cells (e.g. fibroblasts, lymphocytes and stem cells) into proliferation is crucial for tissue repair and regeneration and a key to the growth, development and health of higher multicellular organisms, such as mammals. Quiescence has been a primarily phenotypic description (i.e. non-permanent cell cycle arrest) and poorly studied. However, contrary to the earlier thinking that quiescence is simply a passive and dormant state lacking proliferating activities, recent studies have revealed that cellular quiescence is actively maintained in the cell and that it corresponds to a collection of heterogeneous states. Recent modelling and experimental work have suggested that an Rb-E2F bistable switch plays a pivotal role in controlling the quiescence-proliferation balance and the heterogeneous quiescent states. Other quiescence regulatory activities may crosstalk with and impinge upon the Rb-E2F bistable switch, forming a gene network that controls the cells' quiescent states and their dynamic transitions to proliferation in response to noisy environmental signals. Elucidating the dynamic control mechanisms underlying quiescence may lead to novel therapeutic strategies that re-establish normal quiescent states, in a variety of hyper-and hypo-proliferative diseases, including cancer and ageing.

Hypoxia Induces an Undifferentiated Phenotype of Oral Keratinocytes in vitro

“…Since quiescent cells are recently thought to be distinct from cycling cells or cell cycle arrested cells, we speculate the phenotype seen in hypoxic cell subsets is mainly quiescence showing “a state of cell cycle arrest” that enables cells to re-enter a proliferating state after transient arrest (Yao, 2014). This is supported by the studies on suppression of conversion from arrest to senescence by hypoxia (Blagosklonny, 2013; Leontieva et al, 2012).…”

“…This is supported by the studies on suppression of conversion from arrest to senescence by hypoxia (Blagosklonny, 2013; Leontieva et al, 2012). Moreover, the tendency of diverse patterns of CFSE dye profile under different oxygen tensions could also denote the heterogeneous quiescent states, leading to heterogeneous proliferation (Yao, 2014). …”

In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human peripheral blood lymphocytes

“…Interestingly, by testing much higher hydroquinone concentrations, we observed a relatively weak cytotoxicity in lymphocytes. This was not a surprise, considering that lymphocytes are "stuck" in the G 0 phase of the cell cycle, characterized by the slowing down of many intracellular processes (49,50). The majority of dead cells we detected Jurica K et al In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human lymphocytes Arh Hig Rada Toksikol 2017;68:322-335 using EtBr/AO staining died via apoptosis.…”

Elimination of quiescent slow-cycling cells via reducing quiescence depth by natural compounds purified from Ganoderma lucidum

“…We found that the cytotoxicity in quiescent fibroblasts was associated with the reduction of quiescence depth as indicated by the increased basal activity of the Rb-E2F bistable switch [21–23]. Since quiescence provides a protection against cellular stress and toxicity [24, 25], the shallowing of the quiescence state led to the sensitization of cells to quiescence exit and apoptosis.…”