The analysis, roles and regulation of quiescence in hematopoietic stem cells

Abstract

Tissue homeostasis requires the presence of multipotent adult stem cells that are capable of efficient self-renewal and differentiation; some of these have been shown to exist in a dormant, or quiescent, cell cycle state. Such quiescence has been proposed as a fundamental property of hematopoietic stem cells (HSCs) in the adult bone marrow, acting to protect HSCs from functional exhaustion and cellular insults to enable lifelong hematopoietic cell production. Recent studies have demonstrated that HSC quiescence is regulated by a complex network of cell-intrinsic and -extrinsic factors. In addition, detailed single-cell analyses and novel imaging techniques have identified functional heterogeneity within quiescent HSC populations and have begun to delineate the topological organization of quiescent HSCs. Here, we review the current methods available to measure quiescence in HSCs and discuss the roles of HSC quiescence and the various mechanisms by which HSC quiescence is maintained.

Transient translational quiescence in primordial germ cells

“…The paradigmatic quiescent stem cell is the hematopoietic lineage, which is maintained at a low cell cycle, but can be stimulated to form new blood cells in response to signaling (Valcourt et al, 2012;Nakamura-Ishizu et al, 2014). Recent research has documented that many tissues in human have quiescent stem cells (Rezza et al, 2014), including skeletal muscle (Boonsanay et al, 2016;Fukada et al, 2007), the hair follicle (Morris et al, 2004;Goldstein and Horsley, 2012), the intestine (Richmond et al, 2015a,b) and even the central nervous system (Cheung and Rando, 2013;Webb et al, 2013;Gilboa and Lehmann, 2004).…”

“…Recent research has documented that many tissues in human have quiescent stem cells (Rezza et al, 2014), including skeletal muscle (Boonsanay et al, 2016;Fukada et al, 2007), the hair follicle (Morris et al, 2004;Goldstein and Horsley, 2012), the intestine (Richmond et al, 2015a,b) and even the central nervous system (Cheung and Rando, 2013;Webb et al, 2013;Gilboa and Lehmann, 2004). Unfortunately, quiescent stem cells are also common in cancer and are the bane of chemotherapy; a quiescent cancer stem cell escapes many of the cancer treatments intending to kill the rapidly proliferating cells (Cheung and Rando, 2013;Nakamura-Ishizu et al, 2014). The quiescent cancer stem cells can eventually transition out of quiescence leading to cancer recurrence (Epel, 1967;Pattabiraman and Weinberg, 2014;Tanaka and Dan, 1991).…”

The matrix protein Tiggrin regulates plasmatocyte maturation inDrosophilalarva

“…during neural cell lineages (Farkas and Huttner, 2008;Fichelson et al, 2005) and hematopoiesis (Nakamura-Ishizu et al, 2014). In many cases, cells exit the cell cycle upon terminal differentiation (Buttitta and Edgar, 2007) and perturbations that prolong cell cycle progression result in premature differentiation (Manansala et al, 2013;Tapias et al, 2014).…”

Dynamical Systems Properties of a Mathematical Model for the Treatment of CML

“…The population Q consists of leukemic cells that are quiescent. Some or all of quiescent leukemic cells may be stem cells [14]. When quiescent cells divide, one copy is assumed to be the same kind as the original cell while the second copy may differentiate further into a proliferating type.…”

“…This condition is equivalent to (14). For the underlying biological problem it is natural that an inhibition effect would be smaller than a stimulation effect.…”