Abstract
This article explores and summarizes recent progress in and the characterization of main players in the regulation and cyclic regeneration of hair follicles. The review discusses current views and discoveries on the molecular mechanisms that allow hair follicle stem cells (hfSCs) to synergistically integrate homeostasis during quiescence and activation. Discussion elaborates on a model that shows how different populations of skin stem cells coalesce intrinsic and extrinsic mechanisms, resulting in the maintenance of stemness and hair regenerative potential during an organism’s lifespan. Primarily, we focus on the question of how the intrinsic oscillation of gene networks in hfSCs sense and respond to the surrounding niche environment. The review also investigates the existence of a cell-autonomous mechanism and the reciprocal interactions between molecular signaling axes in hfSCs and niche components, which demonstrates its critical driving force in either the activation of whole mini-organ regeneration or quiescent homeostasis maintenance. These exciting novel discoveries in skin stem cells and the surrounding niche components propose a model of the intrinsic stem cell oscillator which is potentially instructive for translational regenerative medicine. Further studies, deciphering of the distribution of molecular signals coupled with the nature of their oscillation within the stem cells and niche environments, may impact the speed and efficiency of various approaches that could stimulate the development of self-renewal and cell-based therapies for hair follicle stem cell regeneration.
Highlights
Skin is the largest organ, covering the entire human body and extending up to an area of approximately two square meters
We investigate the existence of a cell-autonomous mechanism and the reciprocal interaction between key niche components and key molecular axes in hair follicle stem cells (hfSCs) and the environment, demonstrating its critical driving force in either activation of whole mini-organ regeneration or quiescence homeostasis maintenance
Since the activation with WNT or inhibition with BMP and the fact that signaling could be represented as respective waves (Figures 4B,C), we propose that the intrinsic oscillator in hfSCs has two phases, where each of them follows after the other in a constantly alternating rhythm, with the canonical BMP pathway upstream of WNT signaling (Figure 4B, intrinsic oscillation for BMP either in synergistic or competitive phase) (Kandyba et al, 2013)
Summary
Skin is the largest organ, covering the entire human body and extending up to an area of approximately two square meters. The recent discovery that BMP signaling maintains hfSCs in a dormant telogen, predominantly by inhibition of the canonical WNT signaling pathway, suggests a new model of intrinsic homeostasis regulation of these stem cells (Figure 3B) (Kandyba et al, 2013).
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