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Review
. 2021 Feb 8;148(3):dev165084.
doi: 10.1242/dev.165084.

Stem cell quiescence: the challenging path to activation

Noelia Urbán  1 , Tom H Cheung  2   3   4
Affiliations
Review

Stem cell quiescence: the challenging path to activation

Noelia Urbán et al. Development. .

Abstract

Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity. Quiescence has long been viewed as an inactive state but recent studies have shown that it is in fact an actively regulated process and that adult stem cells are highly reactive to extrinsic stimuli. This has fuelled hopes of boosting the reactivation potential of adult stem cells to improve tissue function during ageing. In this Review, we provide a perspective of the quiescent state and discuss how quiescent adult stem cells transition into the cell cycle. We also discuss current challenges in the field, highlighting recent technical advances that could help overcome some of these challenges.

Keywords: Cell cycle; Developmental biology; Stem cells.

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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Figures

Fig. 1.
Fig. 1.
Cellular states and transitions of adult stem cells. Quiescent adult stem cells can reversibly transition into an active state in which they enter the cell cycle and generate new differentiated cells to maintain tissue homeostasis. In most tissues, stem cells exist in different depths of quiescence (e.g. the deeply quiescent state called dormancy, or a more shallow quiescent state that is primed for activation). During ageing, or when prompted by pathological states, quiescent stem cells can transition into an irreversible senescent (G0) state, therefore hampering the regenerative potential of the tissue.
Fig. 2.
Fig. 2.
The features and molecular regulation of adult stem cell quiescence and activation. Some of the processes that contribute to the activation of quiescent stem cells are depicted. Intron-retained transcripts are accumulated in quiescent stem cells and are processed upon stem cell activation. Important changes in chromatin accessibility have also been reported between quiescent and active stem cells. In addition, key stem cell activation factors, such as MyoD1 and Ascl1, are potent reprogramming factors that harbour the ability to open closed chromatin. Post-transcriptional regulation of gene expression also plays an important role in the quiescent-to-activation transition; this is a process that could be facilitated and/or controlled by phase-separation mechanisms. Finally, protein homeostasis (proteostasis) is emerging as an important regulator of adult stem cells, not only controlling energy metabolism but also the abundance of proteins that act as regulators of the quiescence-to-activation transition.
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