External light activates hair follicle stem cells through eyes via an ipRGC–SCN–sympathetic neural pathway

Fan, Shih-Kang; Chang, Yu-Hao; Chen, Chih-Lung; Wang, Wei‐Hung; Pan, Ming‐Kai; Chen, Wen-Pin; Huang, Wen‐Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V.; Chen, Shih‐Kuo; Lin, Sung‐Jan

doi:10.1073/pnas.1719548115

Cited by 64 publications

(55 citation statements)

References 92 publications

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“…Due to the continuous advance in hair research, more and more cell types (Fig. 2), including DP cells, adipose tissue, lymphatic vessels, nerves and immune cells, are identified to be contributing to the HFSC niche [15,16,[25][26][27][28][29][30][31][32][33][34][35][36], unveiling the complexity and sophistication in the interaction of HFSCs with its environment. Since activating and inhibitory signals can both be present in the HFSC niche, the probability of HFSC activation is the readout of the summation of both activating and inhibitory signals [37,38].…”

Section: Signals and Signaling Cells Within Hfsc Nichementioning

confidence: 99%

“…In catagen, the hair bulb shrinks and the lower portion of the HF regresses through a progressively shortened epithelial strand into the telogen HF. In telogen, HFSCs in the secondary hair germ and bulge remain inactivated local, systemic and even external environmental changes to adjust their activity to meet local and organismal needs [28,34,35,[43][44][45]. Since additional cells of varied functions can be incorporated singly or in combination into the HFSC niche, we think that the niche cells can be modularized and these modules can be co-opted to construct the niche (Fig.…”

Section: Functional Categorization-signaling Sensing and Message-relmentioning

confidence: 99%

“…The piloerection function of HFs relies on the ordered integration of sympathetic nerves and arrector pili muscle around HFs. Sympathetic nerves not only densely surround arrector pili muscle but also loop around HFSCs [34,140]. It is intriguing whether sympathetic nerves around the HFs have dual roles in both piloerection (goosebumps) and HFSC regulation.…”

Section: Signals From Adipose Tissue and Nutritional Sensingmentioning

confidence: 99%

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Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration

et al. 2020

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Stem cell activity is subject to non-cell-autonomous regulation from the local microenvironment, or niche. In adaption to varying physiological conditions and the ever-changing external environment, the stem cell niche has evolved with multifunctionality that enables stem cells to detect these changes and to communicate with remote cells/tissues to tailor their activity for organismal needs. The cyclic growth of hair follicles is powered by hair follicle stem cells (HFSCs). Using HFSCs as a model, we categorize niche cells into 3 functional modules, including signaling, sensing and message-relaying. Signaling modules, such as dermal papilla cells, immune cells and adipocytes, regulate HFSC activity through short-range cell-cell contact or paracrine effects. Macrophages capacitate the HFSC niche to sense tissue injury and mechanical cues and adipocytes seem to modulate HFSC activity in response to systemic nutritional states. Sympathetic nerves implement the message-relaying function by transmitting external light signals through an ipRGC-SCN-sympathetic circuit to facilitate hair regeneration. Hair growth can be disrupted by niche pathology, e.g. dysfunction of dermal papilla cells in androgenetic alopecia and influx of auto-reacting T cells in alopecia areata and lichen planopilaris. Understanding the functions and pathological changes of the HFSC niche can provide new insight for the treatment of hair loss.

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Section: Signals and Signaling Cells Within Hfsc Nichementioning

confidence: 99%

Section: Functional Categorization-signaling Sensing and Message-relmentioning

confidence: 99%

Section: Signals From Adipose Tissue and Nutritional Sensingmentioning

confidence: 99%

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Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration

et al. 2020

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“…Recent studies have also focused on the skin, the other organ exposed to light, but observations are contradictory. While one study reported that light entrainment of skin biorhythms depends on the retina via a neural pathway and is independent of the SCN [4], another has reported that entrainment directly depends on the UV-sensitive neuropsin (OPN5) photopigments that skin cells contain [5].…”

Section: Introductionmentioning

confidence: 99%

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

Vanderstraeten

Gailly

Malkemper

2020

Cell. Mol. Life Sci.

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The mechanisms that synchronize the biorhythms of the mammalian retina with the light/dark cycle are independent of those synchronizing the rhythms in the central pacemaker, the suprachiasmatic nucleus. The identity of the photoreceptor(s) responsible for the light entrainment of the retina of mammals is still a matter of debate, and recent studies have reported contradictory results in this respect. Here, we suggest that cryptochromes (CRY), in particular CRY 2, are involved in that light entrainment. CRY are highly conserved proteins that are a key component of the cellular circadian clock machinery. In plants and insects, they are responsible for the light entrainment of these biorhythms, mediated by the light response of their flavin cofactor (FAD). In mammals, however, no light-dependent role is currently assumed for CRY in light-exposed tissues, including the retina. It has been reported that FAD influences the function of mammalian CRY 2 and that human CRY 2 responds to light in Drosophila, suggesting that mammalian CRY 2 keeps the ability to respond to light. Here, we hypothesize that CRY 2 plays a role in the light entrainment of retinal biorhythms, at least in diurnal mammals. Indeed, published data shows that the light intensity dependence and the wavelength sensitivity commonly reported for that light entrainment fits the light sensitivity and absorption spectrum of light-responsive CRY. We propose experiments to test our hypothesis and to further explore the still-pending question of the function of CRY 2 in the mammalian retina.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…The local circadian clock can affect hair follicle TA cell proliferation (Plikus et al, 2013). Light stimulation of photosensors in the eyes has been shown to induce sympathetic nerves to provoke the release of norepinephrine in the skin which activates hair growth (Fan, Chang, et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Morpho‐regulation in diverse chicken feather formation: Integrating branching modules and sex hormone‐dependent morpho‐regulatory modules

et al. 2018

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Many animals can change the size, shape, texture and color of their regenerated coats in response to different ages, sexes, or seasonal environmental changes. Here we propose that the feather core branching morphogenesis module can be regulated by sex hormones or other environmental factors to change feather forms, textures or colors, thus generating a large spectrum of complexity for adaptation. We use sexual dimorphisms of the chicken to explore the role of hormones. A long-standing question is whether the sex-dependent feather morphologies are autonomously controlled by the male or female cell types, or extrinsically controlled and reversible. We have recently identified core feather branching molecular modules which control the anterior-posterior (BMP, Wnt gradient), medio-lateral (Retinoic signaling, Gremlin), and proximo-distal (Sprouty, BMP) patterning of feathers. We hypothesize that morpho-regulation, through quantitative modulation of existing parameters, can act on core branching modules to topologically tune the dimension of each parameter during morphogenesis and regeneration. Here we explore the involvement of hormones in generating sexual dimorphisms using exogenously delivered hormones. Our strategy is to mimic male androgen levels by applying exogenous dihydrotestosterone and aromatase inhibitors to adult females and to mimic female estradiol levels by injecting exogenous estradiol to adult males. We also examine differentially expressed genes in the feathers of wildtype male and female chickens to identify potential downstream modifiers of feather morphogenesis. The data show male and female feather morphology and their color patterns can be modified extrinsically through molting and resetting the stem cell niche during regeneration.

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External light activates hair follicle stem cells through eyes via an ipRGC–SCN–sympathetic neural pathway

Cited by 64 publications

References 92 publications

Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration

Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals

Morpho‐regulation in diverse chicken feather formation: Integrating branching modules and sex hormone‐dependent morpho‐regulatory modules

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