Intrinsic activation of cell growth and differentiation in ex vivo cultured human hair follicles by a transient endogenous production of ROS

Abstract

The emerging variety of signalling roles for ROS in eukaryotic cells and tissues is currently a matter of intense research. Here we make use of ex vivo cultured single human hair follicles as an experimental model to demonstrate that a transient production of non-lethal endogenous ROS levels in these mini-organs promotes efficiently the entry into the growth phase (anagen). The stimulatory process implicates the specific activation of the hair follicle stem cell niche, encompassing the induction of stem cell differentiation markers (Ck15), overall cell proliferation and sustained growth of the tissue associated with expression of gen targets (Ccnd1) concomitant with the inhibition of Wnt signaling antagonists and repressors (Dkk1, Gsk3β) of Wnt signaling. As a whole, this observation indicates that, once activated, ROS signalling is an intrinsic mechanism regulating the hair follicle stem cell niche independently of any external signal.

Clues that mitochondria are involved in the hair cycle clock: MPZL3 regulates entry into and progression of murine hair follicle cycling

“…This may be important given recent insights into the role of peripheral clock activity in the control of murine and human HF cycling 47,48 . Within mitochondria, MPZL3 interacts with FDXR to promote ROS production, 13 a process shown to influence the HC, 49–52 as well as impact upon circadian clocks 53,54 . Moreover, since it is involved in mitochondrial electron transport and ROS production, 13 MPZL3 lies at the cross‐roads of HC control and HF mitochondrial energy metabolism, 17,19 making it a plausible candidate as a key regulatory molecule within the core HCC.…”

Stem cell‐intrinsic mechanisms regulating adult hair follicle homeostasis

“…160 In line with this result, similar photoactivation treatment in ex vivo cultured human hair follicles cause anagen onset in a Wntdependent manner. 161 The discrepancy in these studies may suggest that long-term ROS has different effects from transient ROS or may be attributed to side effects from different ROS induction methods.…”

Recreation of a hair follicle regenerative microenvironment: Successes and pitfalls

“…Although classically associated with oxidative stress, reactive oxygen species (ROS) at physiological levels play an important role in hair formation. Bulbar epithelial cells produce high amounts of ROS during hair growing 120 and studies using human ex vivo HFs organ cultures proved that transient endogenous ROS production promotes HF stem cell activation and anagen entry, which was associated with the activation of Wnt transcriptional factors 121 . Corroborating these observations, Hamanaka and coworkers 122 showed that mice genetically manipulated to prevent mitochondrial ROS generation in basal epithelium displayed impaired development of epidermis, HF and SG.…”