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Nature Reviews. Disease Primers Mar 2017Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging... (Review)
Review
Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
Topics: Alopecia Areata; Environmental Exposure; Hair; Hair Follicle; Humans; Microbiota; Scalp; Stress, Psychological
PubMed: 28300084
DOI: 10.1038/nrdp.2017.11 -
Current Biology : CB Feb 2009Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social... (Review)
Review
Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social interactions. The hair shaft consists of terminally differentiated keratinocytes that are produced by the hair follicle. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal-mesodermal interactions. After birth, mature and actively growing hair follicles eventually become anchored in the subcutis, and periodically regenerate by spontaneously undergoing repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and relative quiescence (telogen). Our molecular understanding of hair follicle biology relies heavily on mouse mutants with abnormalities in hair structure, growth, and/or pigmentation. These mice have allowed novel insights into important general molecular and cellular processes beyond skin and hair biology, ranging from organ induction, morphogenesis and regeneration, to pigment and stem cell biology, cell proliferation, migration and apoptosis. In this review, we present basic concepts of hair follicle biology and summarize important recent advances in the field.
Topics: Animals; Hair Diseases; Hair Follicle; Mice; Morphogenesis; Stem Cells
PubMed: 19211055
DOI: 10.1016/j.cub.2008.12.005 -
Physiological Reviews Jan 2001Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In... (Review)
Review
Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In this review we have used Chase as our model and tried to put the adult hair follicle growth cycle in perspective. We have tried to sketch the adult hair follicle cycle, as we know it today and what needs to be known. Above all, we hope that this work will serve as an introduction to basic biologists who are looking for a defined biological system that illustrates many of the challenges of modern biology: cell differentiation, epithelial-mesenchymal interactions, stem cell biology, pattern formation, apoptosis, cell and organ growth cycles, and pigmentation. The most important theme in studying the cycling hair follicle is that the follicle is a regenerating system. By traversing the phases of the cycle (growth, regression, resting, shedding, then growth again), the follicle demonstrates the unusual ability to completely regenerate itself. The basis for this regeneration rests in the unique follicular epithelial and mesenchymal components and their interactions. Recently, some of the molecular signals making up these interactions have been defined. They involve gene families also found in other regenerating systems such as fibroblast growth factor, transforming growth factor-beta, Wnt pathway, Sonic hedgehog, neurotrophins, and homeobox. For the immediate future, our challenge is to define the molecular basis for hair follicle growth control, to regenerate a mature hair follicle in vitro from defined populations, and to offer real solutions to our patients' problems.
Topics: Animals; Apoptosis; Body Patterning; Cell Differentiation; Cell Lineage; Cell Movement; Epithelial Cells; Growth Substances; Hair; Hair Follicle; Humans; In Vitro Techniques; Mesoderm; Mice; Morphogenesis; Periodicity; Skin; Stem Cells
PubMed: 11152763
DOI: 10.1152/physrev.2001.81.1.449 -
International Journal of Molecular... Dec 2021Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of... (Review)
Review
Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology. Acromegaly, or GH excess, is associated with hypertrichosis, excessive androgen-independent growth of body hair, and hirsutism in females, while dysfunctional GH receptor-mediated signaling (Laron syndrome) is associated with alopecia and prominent HF defects. The outer root sheath keratinocytes have recently been shown to express functional GH receptors. Furthermore, and contrary to its name, recombinant human GH is known to inhibit female human scalp HFs' growth ex vivo, likely via stimulating the expression of the catagen-inducing growth factor, TGF-β2. These limited available data encourage one to systematically explore the largely uncharted role of GH in human HF biology to uncover nonclassical functions of this core neurohormone in human skin physiology.
Topics: Female; Hair Follicle; Human Growth Hormone; Humans; Receptors, Somatotropin; Skin
PubMed: 34948002
DOI: 10.3390/ijms222413205 -
International Journal of Molecular... Jan 2014Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an... (Review)
Review
Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal β-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated β-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth.
Topics: Animals; Hair Diseases; Hair Follicle; Humans; Morphogenesis; Signal Transduction
PubMed: 24451143
DOI: 10.3390/ijms15011647 -
The EMBO Journal Jun 2021Stem cells are the essential source of building blocks for tissue homeostasis and regeneration. Their behavior is dictated by both cell-intrinsic cues and extrinsic cues... (Review)
Review
Stem cells are the essential source of building blocks for tissue homeostasis and regeneration. Their behavior is dictated by both cell-intrinsic cues and extrinsic cues from the microenvironment, known as the stem cell niche. Interestingly, recent work began to demonstrate that hair follicle stem cells (HFSCs) are not only passive recipients of signals from the surroundings, but also actively send out signals to modulate the organization and function of their own niches. Here, we discuss recent findings, and briefly refer to the old, on the interaction of HFSCs and their niches with the emphasis on the outwards signals from HFSCs toward their niches. We also highlight recent technology advancements that further promote our understanding of HFSC niches. Taken together, the HFSCs emerge as a skin-organizing center rich in signaling output for niche remodeling during various stages of adult skin homeostasis. The intricate crosstalk between HFSCs and their niches adds important insight to skin biology that will inform clinical and bioengineering fields aiming to build complete and functional 3D organotypic cultures for skin replacement therapies.
Topics: Adult Stem Cells; Animals; Cell Communication; Hair Follicle; Homeostasis; Humans; Signal Transduction; Stem Cell Niche
PubMed: 33880808
DOI: 10.15252/embj.2020107135 -
Nature Jun 2020The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily...
The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.
Topics: Animals; Ectoderm; Female; Hair; Hair Color; Hair Follicle; Head; Heterografts; Humans; Mice; Mice, Nude; Organoids; Pluripotent Stem Cells; RNA-Seq; Single-Cell Analysis; Skin; Skin Transplantation
PubMed: 32494013
DOI: 10.1038/s41586-020-2352-3 -
International Journal of Molecular... Sep 2018The functional aspect of scalp hair is not only to protect from solar radiation and heat/cold exposure but also to contribute to one's appearance and personality.... (Review)
Review
The functional aspect of scalp hair is not only to protect from solar radiation and heat/cold exposure but also to contribute to one's appearance and personality. Progressive hair loss has a cosmetic and social impact. Hair undergoes three stages of hair cycle: the anagen, catagen, and telogen phases. Through cyclical loss and new-hair growth, the number of hairs remains relatively constant. A variety of factors, such as hormones, nutritional status, and exposure to radiations, environmental toxicants, and medications, may affect hair growth. Androgens are the most important of these factors that cause androgenic alopecia. Other forms of hair loss include immunogenic hair loss, that is, alopecia areata. Although a number of therapies, such as finasteride and minoxidil, are approved medications, and a few others (e.g., tofacitinib) are in progress, a wide variety of structurally diverse classes of phytochemicals, including those present in ginseng, have demonstrated hair growth-promoting effects in a large number of preclinical studies. The purpose of this review is to focus on the potential of ginseng and its metabolites on the prevention of hair loss and its underlying mechanisms.
Topics: Alopecia; Animals; Hair; Hair Follicle; Humans; Panax; Phytotherapy; Plant Preparations; Signal Transduction
PubMed: 30208587
DOI: 10.3390/ijms19092703 -
Biomedicine & Pharmacotherapy =... May 2021Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair...
Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.
Topics: Alopecia; Androgen Antagonists; Anilides; Animals; Dihydrotestosterone; Disease Models, Animal; Hair Follicle; Male; Mice; Mice, Inbred C57BL; Nitriles; Organ Culture Techniques; Receptors, Androgen; Signal Transduction; Tosyl Compounds
PubMed: 33517191
DOI: 10.1016/j.biopha.2021.111247 -
Annual Review of Cell and Developmental... 2006The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the... (Review)
Review
The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ensure the maintenance of adult skin homeostasis and hair regeneration, but they also participate in the repair of the epidermis after injuries. We summarize here the current knowledge of epidermal SCs of the adult skin. We discuss their fundamental characteristics, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation. Finally, we speculate on how the deregulation of these pathways may lead to cancer formation.
Topics: Animals; Cell Lineage; Epidermal Cells; Epithelium; Hair Follicle; Humans; Morphogenesis; Stem Cells
PubMed: 16824012
DOI: 10.1146/annurev.cellbio.22.010305.104357