Mammalian epidermis consists of three self-renewing compartments: the hair follicle, the sebaceous gland, and the interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close ...relative of the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland, and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, whereas contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell.
Persistent hair loss is a major cause of psychological distress and compromised quality of life in millions of people worldwide. Remarkable progress has been made in understanding the molecular basis ...of hair loss and identifying valid intracellular targets for designing effective therapies for hair loss treatment. Whereas a variety of growth factors and signaling pathways have been implicated in hair cycling process, the activation of Wnt/β-catenin signaling plays a central role in hair follicle regeneration. Several plant-derived chemicals have been reported to promote hair growth by activating Wnt/β-catenin signaling in various in vitro and in vivo studies. This mini-review sheds light on the role of Wnt/β-catenin in promoting hair growth and the current progress in designing hair loss therapies by targeting this signaling pathway.
Platelet-rich plasma (PRP) therapy has been considered as a promising treatment for androgenetic alopecia (AGA). The aim of the study was comparative evaluation of the clinical efficacy of ...PRP-therapy, minoxidil, and their combination in the treatment of men with AGA and to evaluate the effects of PRP on the proliferation of hair follicle (HF) cells in skin biopsy.
The study involved 69 men who were divided into 3 groups who received PRP therapy, minoxidil, and their combination. The clinical efficacy of the therapy was evaluated by the dynamics of morphometric of hairs. To assess cell proliferation antibodies to β-catenin, CD34, Ki67, and to Dkk-1 were used.
PRP treatment was more effective than minoxidil therapy (
= 0.005). Complex therapy turned out to be more effective than minoxidil monotherapy (
< 0.0001) and PRP monotherapy (
= 0.007). After applying PRP the absolute and relative values of the β-catenin and CD34 expression area increased; an increase in Ki67+ index was also significant.
PRP can be considered as a treatment option for AGA. Combined PRP and minoxidil use seems promising for the treatment of AGA. PRP increase in the proliferative activity of HF cells and improves hair morphology in patients with AGA.
Adeno-associated virus (AAV) has been successfully used to deliver gene therapy to improve auditory function in mouse models of hereditary hearing loss. Many forms of hereditary hearing loss have ...mutations which affect the cochlear hair cells, the mechanosensory cells which allow for sound detection and processing. While most conventional AAVs infect inner hair cells (IHCs) with various efficiencies, they infect outer hair cells (OHCs) and supporting cells at lower levels in the cochlea. Here we examine the infection patterns of two synthetic AAVs (AAV2.7m8 and AAV8BP2) in the mouse inner ear. AAV2.7m8 infects both IHCs and OHCs with high efficiency. In addition, AAV2.7m8 infects inner pillar cells and inner phalangeal cells with high efficiency. Our results suggest that AAV2.7m8 is an excellent viral vector for inner ear gene therapy targeting cochlear hair cells and supporting cells, and it will likely greatly expand the potential applications for inner ear gene therapy.
Piloerection (goosebumps) requires concerted actions of the hair follicle, the arrector pili muscle (APM), and the sympathetic nerve, providing a model to study interactions across epithelium, ...mesenchyme, and nerves. Here, we show that APMs and sympathetic nerves form a dual-component niche to modulate hair follicle stem cell (HFSC) activity. Sympathetic nerves form synapse-like structures with HFSCs and regulate HFSCs through norepinephrine, whereas APMs maintain sympathetic innervation to HFSCs. Without norepinephrine signaling, HFSCs enter deep quiescence by down-regulating the cell cycle and metabolism while up-regulating quiescence regulators Foxp1 and Fgf18. During development, HFSC progeny secretes Sonic Hedgehog (SHH) to direct the formation of this APM-sympathetic nerve niche, which in turn controls hair follicle regeneration in adults. Our results reveal a reciprocal interdependence between a regenerative tissue and its niche at different stages and demonstrate sympathetic nerves can modulate stem cells through synapse-like connections and neurotransmitters to couple tissue production with demands.
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•The hair follicle instructs the formation of the APM-sympathetic nerve unit via SHH•APM maintains sympathetic innervation to HFSCs•Sympathetic nerve activates HFSCs via synapse-like contacts and norepinephrine•Cold stimulates not only goosebumps but also hair growth
The arrector pili muscle and the sympathetic neuron form a dual-component niche that regulates hair follicle stem cells—the sympathetic neuron regulates stem cells directly with norepinephrine via synapse-like structures, whereas the arrector pili muscle maintains sympathetic innervation to stem cells. Through these three connected cell types, cold stimulates not only goosebumps but also stem cell activation.
The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells ...influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.
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•Treg activation in skin closely correlates with the HF cycle•Tregs localize to HFSCs and play a major role in HF regeneration•Tregs facilitate HFSC proliferation and differentiation to initiate HF cycling•Treg expression of Jagged 1 is required for efficient hair regeneration
Localized regulatory T cells (Tregs) regulate the hair follicle cycle by driving Notch-dependent stem cell proliferation and differentiation.
Dermoscopic examination of hair and scalp, also named “trichoscopy,” is an essential tool in diagnosis of hair and scalp diseases. Trichoscopy is fast and noninvasive and can be used to evaluate hair ...disorders in all body areas. Body hair disorders are uncommon, and most publications on their dermoscopic features are limited to case reports or series. In this review we present the available information on the dermoscopic diagnosis of body hair disorders including keratosis pilaris, trichostasis spinulosa, pili multigemini, circle hairs, rolled hairs, eruptive vellus hair cyst, and ingrown hairs.
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