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.

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 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 A systematic summary of survival and death signalling during the life of hair follicle stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xi-Min Hu ◽  
Zhi-Xin Li ◽  
Dan-Yi Zhang ◽  
Yi-Chao Yang ◽  
Shen-ao Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Hair Loss ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Hair Follicles ◽  
Model Systems ◽  
Apoptosis Pathway ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

AbstractHair follicle stem cells (HFSCs) are among the most widely available resources and most frequently approved model systems used for studying adult stem cells. HFSCs are particularly useful because of their self-renewal and differentiation properties. Additionally, the cyclic growth of hair follicles is driven by HFSCs. There are high expectations for the use of HFSCs as favourable systems for studying the molecular mechanisms that contribute to HFSC identification and can be applied to hair loss therapy, such as the activation or regeneration of hair follicles, and to the generation of hair using a tissue-engineering strategy. A variety of molecules are involved in the networks that critically regulate the fate of HFSCs, such as factors in hair follicle growth and development (in the Wnt pathway, Sonic hedgehog pathway, Notch pathway, and BMP pathway), and that suppress apoptotic cues (the apoptosis pathway). Here, we review the life cycle, biomarkers and functions of HFSCs, concluding with a summary of the signalling pathways involved in HFSC fate for promoting better understanding of the pathophysiological changes in the HFSC niche. Importantly, we highlight the potential mechanisms underlying the therapeutic targets involved in pathways associated with the treatment of hair loss and other disorders of skin and hair, including alopecia, skin cancer, skin inflammation, and skin wound healing.

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 Establishment of an Efficient Primary Culture System for Human Hair Follicle Stem Cells Using the Rho-Associated Protein Kinase Inhibitor Y-27632

2021 ◽  
Vol 9 ◽  
Author(s):  
Lihong Wen ◽  
Yong Miao ◽  
Zhexiang Fan ◽  
Jiarui Zhang ◽  
Yixuan Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Culture System ◽  
Hair Follicles ◽  
Human Hair Follicle ◽  
Rock Inhibitor ◽  
Hair Follicle Stem Cells ◽  
Human Fibronectin ◽  
Follicle Stem Cells

BackgroundHair follicle tissue engineering is a promising strategy for treating hair loss. Human hair follicle stem cells (hHFSCs), which play a key role in the hair cycle, have potential applications in regenerative medicine. However, previous studies did not achieve efficient hHFSC expansion in vitro using feeder cells. Therefore, there is a need to develop an efficient primary culture system for the expansion and maintenance of hHFSCs.MethodsThe hHFSCs were obtained by two-step proteolytic digestion combined with microscopy. The cell culture dishes were coated with human fibronectin and inoculated with hHFSCs. The hHFSCs were harvested using a differential enrichment procedure. The effect of Rho-associated protein kinase (ROCK) inhibitor Y-27632, supplemented in keratinocyte serum-free medium (K-SFM), on adhesion, proliferation, and stemness of hHFSCs and the underlying molecular mechanisms were evaluated.ResultsThe hHFSCs cultured in K-SFM, supplemented with Y-27632, exhibited enhanced adhesion and proliferation. Additionally, Y-27632 treatment maintained the stemness of hHFSCs and promoted the ability of hHFSCs to regenerate hair follicles in vivo. However, Y-27632-induced proliferation and stemness in hHFSCs were conditional and reversible. Furthermore, Y-27632 maintained propagation and stemness of hHFSCs through the ERK/MAPK pathway.ConclusionAn efficient short-term culture system for primary hHFSCs was successfully established using human fibronectin and the ROCK inhibitor Y-27632, which promoted the proliferation, maintained the stemness of hHFSCs and promoted the ability to regenerate hair follicles in vivo. The xenofree culturing method used in this study provided a large number of high-quality seed cells, which have applications in hair follicle tissue engineering and stem cell therapy.

scholarly journals Adult hair follicles keep oncogenic growth in check

2019 ◽  
Vol 218 (10) ◽  
pp. 3163-3165
Author(s):  
Denise Gay ◽  
Mayumi Ito
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Somatic Mutations ◽  
Hair Follicles ◽  
Management Technique ◽  
Normal Cells ◽  
Cell Biol ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Recent research shows that potentially cancerous, somatic mutations can reside in normal cells. Pineda et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201907178) report on a unique management technique by hair follicle stem cells to evade tumorigenesis.

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 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 Polycomb repressive complex 2 in adult hair follicle stem cells is dispensable for hair regeneration

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009948
Author(s):  
Pooja Flora ◽  
Meng-Yen Li ◽  
Phillip M. Galbo ◽  
Maider Astorkia ◽  
Deyou Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Activated State ◽  
Hair Regeneration ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Hair follicle stem cells (HFSCs) are multipotent cells that cycle through quiescence and activation to continuously fuel the production of hair follicles. Prior genome mapping studies had shown that tri-methylation of histone H3 at lysine 27 (H3K27me3), the chromatin mark mediated by Polycomb Repressive Complex 2 (PRC2), is dynamic between quiescent and activated HFSCs, suggesting that transcriptional changes associated with H3K27me3 might be critical for proper HFSC function. However, functional in vivo studies elucidating the role of PRC2 in adult HFSCs are lacking. In this study, by using in vivo loss-of-function studies we show that, surprisingly, PRC2 plays a non-instructive role in adult HFSCs and loss of PRC2 in HFSCs does not lead to loss of HFSC quiescence or changes in cell identity. Interestingly, RNA-seq and immunofluorescence analyses of PRC2-null quiescent HFSCs revealed upregulation of genes associated with activated state of HFSCs. Altogether, our findings show that transcriptional program under PRC2 regulation is dispensable for maintaining HFSC quiescence and hair regeneration.

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