scholarly journals Roles of Melatonin in Goat Hair Follicle Stem Cell Proliferation and Pluripotency Through Regulating the Wnt Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Weidong Zhang ◽  
Niu Wang ◽  
Tongtong Zhang ◽  
Meng Wang ◽  
Wei Ge ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Wnt Signaling Pathway ◽  
Hematopoietic Progenitor Cell ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells ◽  
The Impact

Emerging studies show that melatonin promotes cashmere development through hypodermic implantation. However, the impact and underlying mechanisms are currently unknown. In vitro study has previously demonstrated that melatonin induces cashmere growth by regulating the proliferation of goat secondary hair follicle stem cells (gsHFSCs), but there is limited information concerning the effects of melatonin on cell pluripotency. It is also known that Wnt signaling may actively participate in regulating cell proliferation and stem cell pluripotency. Therefore, in the current investigation, goat hair follicle stem cells were exposed to multiple concentrations of melatonin and different culture times to reveal the relationship between melatonin and the activation of Wnt signaling. A proportionally high Catenin beta-1 (CTNNB1) response was induced by 500 ng/L of melatonin, but it was then suppressed with the dosages over 1,000 ng/L. Greater amounts of CTNNB1 entered the cell nuclei by extending the exposure time to 72 h, which activated transcription factor 4/lymphoid enhancer-binding factor 1 and promoted the expression of the proliferation-related genes C-MYC, C-JUN, and CYCLIND1. Moreover, nuclear receptor ROR-alpha (RORα) and bone morphogenetic protein 4 (BMP4) were employed to analyze the underlying mechanism. RORα presented a sluggish concentration/time-dependent rise, but BMP4 was increased dramatically by melatonin exposure, which revealed that melatonin might participate in regulating the pluripotency of hair follicle stem cells. Interestingly, NOGGIN, which is a BMP antagonist and highly relevant to cell stemness, was also stimulated by melatonin. These findings demonstrated that melatonin exposure and/or NOGGIN overexpression in hair follicle stem cells might promote the expression of pluripotency markers Homeobox protein NANOG, Organic cation/carnitine transporter 4, and Hematopoietic progenitor cell antigen CD34. Our findings here provided a comprehensive view of Wnt signaling in melatonin stimulated cells and melatonin mediated stemness of gsHFSCs by regulating NOGGIN, which demonstrates a regulatory mechanism of melatonin enhancement on the growth of cashmere.

scholarly journals Mechanotransductive Differentiation of Hair Follicle Stem Cells Derived from Aged Eyelid Skin into Corneal Endothelial-Like Cells

2021 ◽  
Author(s):  
Christian Olszewski ◽  
Jessika Maassen ◽  
Rebecca Guenther ◽  
Claudia Skazik-Voogt ◽  
Angela Gutermuth
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Adherent Cell ◽  
Promising Alternative ◽  
Eyelid Skin ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

AbstractCorneal endothelial insufficiency is one of the leading causes of blindness. The main contemporary treatment for corneal blindness is endothelial keratoplasty, which, however, is unsatisfactory as a medical therapy due to the lack of donor corneas and graft rejection. Therefore, autologous stem cell-based corneal endothelial tissue substitutes may be a promising alternative to conventional grafts in the future. To address the age of most patients suffering from corneal endothelial deficiencies, we investigated the presence and potential of hair-derived stem cells from older tissue donors. Our studies revealed the presence of pluripotency- and neural crest-associated markers in tissue sections from blepharoplasty patients aged 50 to 80 years. In vitro outgrowths from eyelid hair follicles on collagen-coated tissue culture plates revealed a weak decrease in stem-cell potency. In contrast, cells within the spheres that spontaneously formed from the adherent cell layer retained full stem-cell potency and could be differentiated into cells of the ecto- meso and endodermal lineages. Although these highly potent hair follicle derived stem cells (HFSC) were only very slightly expandable, they were able to recognize the biomimicry of the Descemet’s-like topography and differentiate into corneal endothelial-like cells. In conclusion, HFSCs derived from epidermal skin of eyelid biopsies are a promising cell source to provide autologous corneal endothelial replacement for any age group of patients. Graphical Abstract

scholarly journals Escape of hair follicle stem cells causes stem cell exhaustion during aging

Nature Aging ◽  
2021 ◽  
Vol 1 (10) ◽  
pp. 889-903
Author(s):  
Chi Zhang ◽  
Dongmei Wang ◽  
Jingjing Wang ◽  
Li Wang ◽  
Wenli Qiu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Exhaustion ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

scholarly journals Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zijian Xu ◽  
Wenjie Wang ◽  
Kaiju Jiang ◽  
Zhou Yu ◽  
Huanwei Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Stem Cell Markers ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation.

scholarly journals Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling

2016 ◽  
Vol 113 (11) ◽  
pp. E1498-E1505 ◽  
Author(s):  
Xinhong Lim ◽  
Si Hui Tan ◽  
Ka Lou Yu ◽  
Sophia Beng Hui Lim ◽  
Roeland Nusse
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Extended Period ◽  
Lineage Tracing ◽  
Hair Cycle ◽  
Cell Potential ◽  
Differentiated Cells ◽  
Hair Follicle Stem Cells

How stem cells maintain their identity and potency as tissues change during growth is not well understood. In mammalian hair, it is unclear how hair follicle stem cells can enter an extended period of quiescence during the resting phase but retain stem cell potential and be subsequently activated for growth. Here, we use lineage tracing and gene expression mapping to show that the Wnt target gene Axin2 is constantly expressed throughout the hair cycle quiescent phase in outer bulge stem cells that produce their own Wnt signals. Ablating Wnt signaling in the bulge cells causes them to lose their stem cell potency to contribute to hair growth and undergo premature differentiation instead. Bulge cells express secreted Wnt inhibitors, including Dickkopf (Dkk) and secreted frizzled-related protein 1 (Sfrp1). However, the Dickkopf 3 (Dkk3) protein becomes localized to the Wnt-inactive inner bulge that contains differentiated cells. We find that Axin2 expression remains confined to the outer bulge, whereas Dkk3 continues to be localized to the inner bulge during the hair cycle growth phase. Our data suggest that autocrine Wnt signaling in the outer bulge maintains stem cell potency throughout hair cycle quiescence and growth, whereas paracrine Wnt inhibition of inner bulge cells reinforces differentiation.

scholarly journals Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury

2011 ◽  
Vol 22 (14) ◽  
pp. 2532-2540 ◽  
Author(s):  
Kerry-Ann Nakrieko ◽  
Alena Rudkouskaya ◽  
Timothy S. Irvine ◽  
Sudhir J. A. D'souza ◽  
Lina Dagnino
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Stem Cell Population ◽  
Epidermal Surface ◽  
Hair Follicle Stem Cells ◽  
Integrin Linked Kinase ◽  
Hair Follicle Growth ◽  
Follicle Stem Cells

Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15–expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

scholarly journals Extracellular caspase-1 regulates hair follicle stem cell migration during wound-healing

2019 ◽  
Author(s):  
Subhasri Ghosh ◽  
Akhil SHP Ananthan ◽  
Sunny Kataria ◽  
Neha Pincha ◽  
Abhik Dutta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Hair Follicle ◽  
Healing Process ◽  
Environmental Cues ◽  
Macromolecular Complex ◽  
Caspase 1 ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

AbstractMigration of stem cells from one niche to another is a fundamental behavior observed during tissue morphogenesis, homeostasis, and repair 1. A common thread running throughout these phenomena is the ability of stem cells to sense their environmental cues that, in turn, regulate their spatiotemporal localization with amazing precision. Perturbations of such cellular responses underlie a spectrum of pathologies ranging from developmental defects, tumor metastasis and ineffective wound closure 2,3. In somatic tissues, the wound-healing process is a paradigm of the directed migration of various stem cell pools to the site of injury where they differentiate to replenish lost or damaged cells. While there has been substantial investment and progress in understanding the lineage trajectory of stem cells once they reach their destination, comparatively little is understood regarding the mechanisms guiding their chemotactic journey to the wound site. In the context of the skin, it has been shown nearly two decades ago that wounding activates various local epithelial stem cell pools, including multipotent hair follicle stem cells, to infiltrate the epidermis where they participate in the reconstruction of the damaged tissue 4,5. However, elucidation of the environmental cues that coax these cells out of their hair follicle niche to the damaged epidermis has proven to be an intractable problem to solve. Using both an excisional wound and genetic mouse models of wound healing, we discovered that wounded keratinocytes secrete the enzyme Caspase-1. This protein is classically known as a critical component of the cytosolic macromolecular complex called an inflammasome that mediates the unconventional secretion of various cytokines including IL-1a 6. Surprisingly, we find that the released caspase-1 itself has a non-canonical role in the extracellular milieu. Through the Caspase Activation Recruitment Domain (CARD) of caspase-1, this protein is sufficient to initiate chemotaxis of hair follicle stem cells into the epidermis. The secretion of caspase-1 has also been documented in many other pathological scenarios7,8 and we observed that the migration of HFSCs into the epidermis following UV irradiation of the skin is also caspase-1 dependent. Uncovering this novel function of Caspase-1 facilitates a deeper understanding of the mechanistic basis of the epithelial hyperplasia found to accompany numerous inflammatory skin diseases.

scholarly journals A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells

2020 ◽  
Author(s):  
Rajiv L Tiwari ◽  
Pratibha Mishra ◽  
Nicola Martin ◽  
Nikhil Oommen George ◽  
Vadim Sakk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Canonical Wnt Signaling ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Elevated Activity ◽  
Canonical Wnt ◽  
Follicle Stem Cells

SummaryNormal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.

scholarly journals A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells

2020 ◽  
Author(s):  
Rajiv Tiwari ◽  
Pratibha Mishra ◽  
Nicola Martin ◽  
Nikhil George ◽  
Vadim Sakk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Hair Follicle ◽  
Canonical Wnt Signaling ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Elevated Activity ◽  
Canonical Wnt ◽  
Follicle Stem Cells

Abstract Normal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.

scholarly journals An Intrinsic Oscillation of Gene Networks Inside Hair Follicle Stem Cells: An Additional Layer That Can Modulate Hair Stem Cell Activities

2020 ◽  
Vol 8 ◽  
Author(s):  
Patrycja Daszczuk ◽  
Paula Mazurek ◽  
Tomasz D. Pieczonka ◽  
Alicja Olczak ◽  
Łukasz M. Boryń ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Hair Follicles ◽  
Hair Follicle Stem Cells ◽  
Intrinsic Oscillation ◽  
Follicle Stem Cells ◽  
Niche Components

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.

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