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Experimental & Molecular Medicine Feb 2024Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The... (Review)
Review
Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The crucial function of hair follicle stem cells is to maintain these hair growth cycles. Another vital aspect is the activity of melanocyte stem cells, which differentiate into melanin-producing melanocytes, contributing to skin and hair pigmentation. Sebaceous gland stem cells also have a pivotal role in maintaining the skin barrier by regenerating mature sebocytes. These stem cells are maintained in a specialized microenvironment or niche and are regulated by internal and external signals, determining their dynamic behaviors in homeostasis and hair follicle regeneration. The activity of these stem cells is tightly controlled by various factors secreted by the niche components around the hair follicles, as well as immune-mediated damage signals, aging, metabolic status, and stress. In this study, we review these diverse stem cell regulatory and related molecular mechanisms of hair regeneration and disease conditions. Molecular insights would provide new perspectives on the disease mechanisms as well as hair and skin disorder treatment.
Topics: Animals; Hair Follicle; Hair; Skin; Melanocytes; Stem Cells; Mammals
PubMed: 38182654
DOI: 10.1038/s12276-023-01151-5 -
International Journal of Molecular... May 2022Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. Although it has been studied extensively in... (Review)
Review
Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. Although it has been studied extensively in cutaneous melanoma, the role of MITF in uveal melanoma (UM) has not been explored in much detail. We review the literature about the role of MITF in normal melanocytes, in cutaneous melanoma, and in UM. In normal melanocytes, MITF regulates melanocyte development, melanin synthesis, and melanocyte survival. The expression profile and the behaviour of MITF-expressing cells suggest that MITF promotes local proliferation and inhibits invasion, inflammation, and epithelial-to-mesenchymal (EMT) transition. Loss of MITF expression leads to increased invasion and inflammation and is more prevalent in malignant cells. Cutaneous melanoma cells switch between MITF-high and MITF-low states in different phases of tumour development. In UM, MITF loss is associated with loss of BAP1 protein expression, which is a marker of poor prognosis. These data indicate a dual role for MITF in benign and malignant melanocytic cells.
Topics: Humans; Inflammation; Melanocytes; Melanoma; Microphthalmia-Associated Transcription Factor; Skin Neoplasms; Uveal Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35682684
DOI: 10.3390/ijms23116001 -
Cells Jun 2022Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of... (Review)
Review
Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of melanin and are transferred from melanocytes to keratinocytes. The relatively well-known process by which melanin is synthesized from melanocytes is known as melanogenesis. The relationship between melanogenesis and autophagy is attracting the attention of researchers because proteins associated with autophagy, such as WD repeat domain phosphoinositide-interacting protein 1, microtubule-associated protein 1 light chain 3, autophagy-related (ATG)7, ATG4, beclin-1, and UV-radiation resistance-associated gene, contribute to the melanogenesis signaling pathway. Additionally, there are reports that some compounds used as whitening cosmetics materials induce skin depigmentation through autophagy. Thus, the possibility that autophagy is involved in the removal of melanin has been suggested. To date, however, there is a lack of data on melanosome autophagy and its underlying mechanism. This review highlights the importance of autophagy in melanin homeostasis by providing an overview of melanogenesis, autophagy, the autophagy machinery involved in melanogenesis, and natural compounds that induce autophagy-mediated depigmentation.
Topics: Autophagy; Homeostasis; Melanins; Melanocytes; Melanosomes
PubMed: 35805169
DOI: 10.3390/cells11132085 -
International Journal of Molecular... Apr 2021The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and... (Review)
Review
The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and protect the skin from adverse effects of ultraviolet radiation (UVR) and oxidative stress from various environmental pollutants. Melanocytes reside in the basal layer of the interfollicular epidermis and are compensated by melanocyte stem cells in the follicular bulge area. Various stimuli such as eczema, microbial infection, ultraviolet light exposure, mechanical injury, and aging provoke skin inflammation. These acute or chronic inflammatory responses cause inflammatory cytokine production from epidermal keratinocytes as well as dermal fibroblasts and other cells, which in turn stimulate melanocytes, often resulting in skin pigmentation. It is confirmed by some recent studies that several interleukins (ILs) and other inflammatory mediators modulate the proliferation and differentiation of human epidermal melanocytes and also promote or inhibit expression of melanogenesis-related gene expression directly or indirectly, thereby participating in regulation of skin pigmentation. Understanding of mechanisms of skin pigmentation due to inflammation helps to elucidate the relationship between inflammation and skin pigmentation regulation and can guide development of new therapeutic pathways for treating pigmented dermatosis. This review covers the mechanistic aspects of skin pigmentation caused by inflammation.
Topics: Aging; Cell Differentiation; Humans; Inflammation; Keratinocytes; Melanins; Melanocytes; Skin; Skin Pigmentation; Ultraviolet Rays
PubMed: 33921371
DOI: 10.3390/ijms22083970 -
Pigment Cell & Melanoma Research Nov 2023Melanocyte stem cells (McSCs) of the hair follicle are necessary for hair pigmentation and can serve as melanoma cells of origin when harboring cancer-driving mutations....
Melanocyte stem cells (McSCs) of the hair follicle are necessary for hair pigmentation and can serve as melanoma cells of origin when harboring cancer-driving mutations. McSCs can be released from quiescence, activated, and undergo differentiation into pigment-producing melanocytes during the hair cycle or due to environmental stimuli, such as ultraviolet-B (UVB) exposure. However, our current understanding of the mechanisms regulating McSC stemness, activation, and differentiation remains limited. Here, to capture the differing possible states in which murine McSCs can exist, we sorted melanocyte nuclei from quiescent (telogen) skin, skin actively producing hair shafts (anagen), and skin exposed to UVB. With these sorted nuclei, we then utilized single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing (snATAC-seq) and characterized three melanocyte lineages: quiescent McSCs (qMcSCs), activated McSCs (aMcSCs), and differentiated melanocytes (dMCs) that co-exist in all three skin conditions. Furthermore, we successfully identified differentially accessible genes and enriched transcription factor binding motifs for each melanocyte lineage. Our findings reveal potential gene regulators that determine these melanocyte cell states and provide new insights into how aMcSC chromatin states are regulated differently under divergent intrinsic and extrinsic cues. We also provide a publicly available online tool with a user-friendly interface to explore this comprehensive dataset, which will provide a resource for further studies on McSC regulation upon natural or UVB-mediated stem cell activation.
Topics: Mice; Animals; Chromatin; Melanocytes; Skin; Hair Follicle; Stem Cells; Cell Differentiation
PubMed: 37462349
DOI: 10.1111/pcmr.13112 -
Clinics in Dermatology 2021Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that has the potential to revolutionize dermatology. Extensive research in this area in conjunction... (Review)
Review
Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that has the potential to revolutionize dermatology. Extensive research in this area in conjunction with the recent assignment of reimbursement codes has made the clinical use of this technology a practical reality. Though there is awareness and use of this technology at large academic centers, a knowledge gap still remains in interpreting RCM images among the dermatology community. We review the key RCM features of melanocytic and nonmelanocytic lesions to provide guidance in distinguishing benign entities from malignant dermatologic neoplasms.
Topics: Dermoscopy; Humans; Melanocytes; Microscopy, Confocal; Skin Neoplasms
PubMed: 34809769
DOI: 10.1016/j.clindermatol.2021.03.010 -
Current Opinion in Cell Biology Dec 2020Melanocytes are neuroectoderm-derived pigment-producing cells with highly polarized dendritic morphology. They protect the skin against ultraviolet radiation by... (Review)
Review
Melanocytes are neuroectoderm-derived pigment-producing cells with highly polarized dendritic morphology. They protect the skin against ultraviolet radiation by providing melanin to neighbouring keratinocytes. However, the mechanisms underlying melanocyte polarization and its relevance for diseases remain mostly elusive. Numerous studies have instead revealed roles for polarity regulators in other neuroectoderm-derived lineages including different neuronal cell types. Considering the shared ontogeny and morphological similarities, these lineages may be used as reference models for the exploration of melanocyte polarity, for example, regarding dendrite formation, spine morphogenesis and polarized organelle transport. In this review, we summarize and compare the latest progress in understanding polarity regulation in neuronal cells and melanocytes and project key open questions for future work.
Topics: Cell Differentiation; Cell Lineage; Cell Polarity; Humans; Keratinocytes; Melanocytes; Melanosomes; Neural Plate
PubMed: 33099084
DOI: 10.1016/j.ceb.2020.09.001 -
International Journal of Molecular... Nov 2022cAMP-PKA signaling plays a pivotal role in melanin synthesis and melanosome transport by responding to the binding of the α-melanocyte-stimulating hormone (α-MSH) to...
cAMP-PKA signaling plays a pivotal role in melanin synthesis and melanosome transport by responding to the binding of the α-melanocyte-stimulating hormone (α-MSH) to melanocortin-1 receptor (MC1R). Adenylate cyclases (ADCYs) are the enzymes responsible for the synthesis of cAMP from ATP, which comprises nine transmembrane isoforms (ADCYs 1-9) and one soluble adenylate cyclase (ADCY 10) in mammals. However, little is known about which and how ADCY isoforms regulate melanocyte generation, melanin biosynthesis, and melanosome transport in vivo. In this study, we have generated a series of single and double mutants of Adcy isoforms in zebrafish. Among them, and double mutants cause defects in melanosome dispersion but do not impair melanoblast differentiation and melanocyte regeneration during the embryonic or larval stages. Activation of PKA, the main effector of cAMP signaling, significantly ameliorates the defects in melanosome dispersion in and double mutants. Mechanistically, Adcy3a and Adcy5 regulate melanosome dispersion by activating kinesin-1 while inhibiting cytoplasmic dynein-1. In adult zebrafish, Adcy3a and Adcy5 participate in the regulation of the expression of microphthalmia transcription factor (Mitfa) and melanin synthesis enzymes Tyr, Dct, and Trp1b. The deletion of Adcy3a and Adcy5 inhibits melanin production and reduces pigmented melanocyte numbers, causing a defect in establishing adult melanocyte stripes. Hence, our studies demonstrate that Adcy3a and Adcy5 play essential but redundant functions in mediating α-MSH-MC1R/cAMP-PKA signaling for regulating melanin synthesis and melanosome dispersion.
Topics: Animals; Melanosomes; Zebrafish; Melanins; alpha-MSH; Melanocytes; Receptor, Melanocortin, Type 1; Mammals
PubMed: 36430661
DOI: 10.3390/ijms232214182 -
The American Journal of Pathology Nov 2019Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases,... (Review)
Review
Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have been recognized to have an etiopathogenetic role in the development and progression of precursor melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor/MET (HGF/MET) axis is emerging as a critical player not only in the tumor itself but also in the immune microenvironment in which the tumor grows and advances in its development. Moreover, the activation of this pathway has emerged as a paradigm of tumor resistance to modern targeted therapies, and the assessment of its expression in patients' samples may be a valuable biomarker of tumor progression and response to targeted therapy. Here we summarize our current understanding of this important receptor tyrosine kinase in normal melanocyte proliferation/motility, in tumor progression and metastasis, its genetic alterations in certain subtype of melanocytic lesions, and how its pathway has been explored for the development of selective inhibitors.
Topics: Animals; Cell Movement; Cell Proliferation; Hepatocyte Growth Factor; Humans; Melanocytes; Melanoma; Proto-Oncogene Proteins c-met; Signal Transduction; Skin Neoplasms; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 31476283
DOI: 10.1016/j.ajpath.2019.08.002 -
The American Journal of Dermatopathology Sep 2022In dermal melanocytoses such as blue nevus or nevus of Ota, an ultrastructural study has demonstrated an intimate relationship between the dendritic melanocytes and the...
In dermal melanocytoses such as blue nevus or nevus of Ota, an ultrastructural study has demonstrated an intimate relationship between the dendritic melanocytes and the dermal elastic fibers with elongated cytoplasmic processes of the melanocytes aligning lengthwise along the axis of the elastic fibers in longitudinal sections and encircling the elastic fibers in cross-sections. Such a close arrangement has not been reported in common melanocytic nevi. The current case described a similar arrangement between the melanocytes and the dermal elastic fibers in a usual intradermal melanocytic nevus. Of note, as the melanocytes matured with descent, the deep melanocytes were arranged in single cells embracing the elastic fibers, imparting a signet-ring cell/phagocytosis appearance. A Verhoeff-van Gieson stain showed hypertrophy of the melanocyte-associated elastic fibers compared with the elastic fibers in the dermal background, suggesting a paracrine or juxtracrine interaction between the melanocytes and the dermal cellular components. Because of the distinctive affinity of the melanocytes to the dermal elastic fibers in this melanocytic lesion, the term melanocytic nevus with elastophilic features is suggested for this peculiar melanocytic variant.
Topics: Humans; Melanocytes; Nevus; Nevus, Epithelioid and Spindle Cell; Nevus, Pigmented; Skin Neoplasms
PubMed: 35503877
DOI: 10.1097/DAD.0000000000002207