Modulatory effects of oxytocin on normal human cultured melanocyte proliferation, migration, and melanogenesis.

Melanocytes are specialized melanin-producing neural crest-derived cells. Melanocyte proliferation and melanin production (i.e., melanogenesis) are crucial for determining skin color. Disruption of these processes can cause pigmentary skin disorders, including hypo-pigmentary disorders such as vitiligo and hyper-pigmentary disorders such as melasma. Understanding these processes is important for discovering new targets to tackle these skin disorders. Therefore, this study aimed to investigate the effects of oxytocin (OXT) on melanocyte functions. Normal Human Cultured Melanocytes (NHCM) were treated with different OXT doses to investigate OXT effects and mechanisms on NHCM proliferation, migration, and on melanogenesis. OXT significantly increased NHCM proliferation and migration in a dose-dependent manner after 72 h of treatment. In addition, OXT dose-dependently upregulated melanogenesis-related microphtalmia-associated transcription factor, tyrosinase, tyrosinase-related protein (TYRP)-1, and TYRP-2 expression accompanied by an increased trend in melanosome number and maturation stage. Furthermore, OXT at concentrations (62.5-125 nM) increased melanin production. These findings suggest the involvement of OXT receptor (OXTR). In addition, this study demonstrates that OXT stimulates melanocyte proliferation, migration, with a tendency toward melanosome maturation, while it modulates melanin production in a dose-dependent manner. Thus, OXT system including its receptor OXTR may be a potential therapeutic target for skin pigmentary disorders.

LL37-DNA Complex Drives Vitiligo Progression Through TLR9-MyD88 Signaling Pathways.

Vitiligo is an autoimmune disorder characterized by chronic depigmentation and milk-white patches on the skin. Skin infiltration by autoreactive CD8+ T cells causes melanocyte destruction in vitiligo. Multiple risk factors, particularly immune-related inflammatory factors, are involved in the disappearance of melanocytes. LL37 is a classic damage-associated molecular pattern molecule that is involved in the development of various autoimmune diseases. An enhanced expression of LL37 in vitiligo is known; however, the exact role of LL37 in melanocyte loss has not yet been elucidated. In the present study, we detected increased LL37 expression in vitiligo serum and lesions. Furthermore, we confirmed that cultured keratinocytes released LL37 after treatment with H2O2. Moreover, the LL37-DNA complex enhanced the secretion of CXCL9, CXCL10, and CXCL16 from keratinocytes via the TLR9-MyD88 signaling pathway and facilitated the migration of CD8+ T cells. Altogether, our study demonstrates that LL37 released from keratinocytes binds to DNA and contributes to melanocyte destruction under oxidative stress-induced autoimmunity in vitiligo.

A novel liquid plasma derivative inhibits melanogenesis through upregulation of Nrf2.

Non-thermal plasma (NTP) is an emerging technology with extensive applications in biomedicine, including treatment of abnormal pigmentation. However, very few studies have investigated how plasma induces anti-melanogenesis. Here, liquid plasma was prepared by treating an NTP jet with helium and oxygen (as carrier gases) for 15 min in serum-free culture media. In the zebrafish model, pigmentation ratio was observed with or without liquid plasma. The anti-melanogenic effect of liquid plasma was evaluated in human melanocytes by assessing the expression of melanogenesis-related genes using western blotting, RT-PCR, and immunohistochemistry. Liquid plasma reduced pigmentation in the zebrafish model and inhibited melanin synthesis in primary human melanocytes. Intracellular reactive oxygen species levels decreased and Nrf2 expression increased in liquid plasma-treated melanocytes. Liquid plasma affected microphthalmia-associated transcription factor (MITF) and tyrosinase mRNA and protein levels, tyrosinase activity, and melanin content. Considering the role of Wnt/ß-catenin and PI3K/Akt pathways in melanogenesis, the effect of liquid plasma on this pathway was determined; liquid plasma decreased active ß-catenin, LEF1/TCF4, MITF, and tyrosinase levels in a time-dependent manner and inhibited the nuclear translocation of ß-catenin. This inhibition subsequently suppressed melanogenesis by downregulating MITF and tyrosinase. These results suggest that liquid plasma may be used for treating pigmentary disorders.

Vitiligo: From Pathogenesis to Treatment.

Recent advances in vitiligo have provided promising treatment options, particularly through understanding the immune-mediated mechanisms leading to depigmentation. The inflammatory components in both vitiligo (non-segmental) and segmental vitiligo have similarities. Both are believed to result from an immune-based destruction of melanocytes by anti-melanocyte-specific cytotoxic T cells. The JAK-STAT pathway is activated with IFN-γ as the crucial cytokine and Th1-associated chemokines such as CXCL9 and CXCL10 recruit immune cells towards vitiligo skin. Nonetheless, clear differences are also present, such as the localized nature of segmental vitiligo, likely due to somatic mosaicism and increased presence of poliosis. The differing prevalence of poliosis suggests that the follicular immune privilege, which is known to involve immune checkpoints, may be more important in vitiligo (non-segmental). Immunomodulatory therapies, especially those targeting the JAK-IFNγ pathway, are currently at the forefront, offering effective inhibition of melanocyte destruction by cytotoxic T cells. Although Janus Kinase (JAK) inhibitors demonstrate high repigmentation rates, optimal results can take several months to years. The influence of environmental UV exposure on repigmentation in patients receiving immunomodulating drugs remains largely underexplored. Nonetheless, the combined effect of phototherapy with JAK inhibitors is impressive and suggests a targeted immune-based treatment may still require additional stimulation of melanocytes for repigmentation. Identifying alternative melanocyte stimulants beyond UV light remains crucial for the future management of vitiligo.

Retinoic acid, an essential component of the roof plate organizer, promotes the spatiotemporal segregation of dorsal neural fates.

Dorsal neural tube-derived retinoic acid promotes the end of neural crest production and transition into a definitive roof plate. Here, we analyze how this impacts the segregation of central and peripheral lineages, a process essential for tissue patterning and function. Localized in ovo inhibition in quail embryos of retinoic acid activity followed by single-cell transcriptomics unraveled a comprehensive list of differentially expressed genes relevant to these processes. Importantly, progenitors co-expressed neural crest, roof plate and dI1 interneuron markers, indicating a failure in proper lineage segregation. Furthermore, separation between roof plate and dI1 interneurons is mediated by Notch activity downstream of retinoic acid, highlighting their crucial role in establishing the roof plate-dI1 boundary. Within the peripheral branch, where absence of retinoic acid resulted in neural crest production and emigration extending into the roof plate stage, sensory progenitors failed to separate from melanocytes, leading to formation of a common glia-melanocyte cell with aberrant migratory patterns. In summary, the implementation of single-cell RNA sequencing facilitated the discovery and characterization of a molecular mechanism responsible for the segregation of dorsal neural fates during development.

The biochemistry of melanogenesis: an insight into the function and mechanism of melanogenesis-related proteins.

Melanin is an amino acid derivative produced by melanocyte through a series of enzymatic reactions using tyrosinase as substrate. Human skin and hair color is also closely related to melanin, so understanding the mechanisms and proteins that produce melanin is very important. There are many proteins involved in the process of melanin expression, For example, proteins involved in melanin formation such as p53, HNF-1α (Hepatocyte nuclear factor 1α), SOX10 (Sry-related HMg-Box gene 10) and pax3 (paired box gene 3), MC1R(Melanocortin 1 Receptor), MITF (Microphthalmia-associated transcription factor), TYR (tyrosinase), TYRP1 (tyrosinase-related protein-1), TYRP2 (tyrosinase-related protein-2), and can be regulated by changing their content to control the production rate of melanin. Others, such as OA1 (ocular albinism type 1), Par-2 (protease-activated receptor 2) and Mlph (Melanophilin), have been found to control the transfer rate of melanosomes from melanocytes to keratinocytes, and regulate the amount of human epidermal melanin to control the depth of human skin color. In addition to the above proteins, there are other protein families also involved in the process of melanin expression, such as BLOC, Rab and Rho. This article reviews the origin of melanocytes, the related proteins affecting melanin and the basic causes of related gene mutations. In addition, we also summarized the active ingredients of 5 popular whitening cosmetics and their mechanisms of action.

An In Vivo Study of LNS8801, a GPER Agonist, in a Spontaneous Melanoma-Prone Mouse Model, TGS.

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic exposure to sunlight. Over the course of the 32-week experiment, visible images were taken by the small animal imaging IVIS system to track tumor progression, and blood and tissue samples were collected for molecular analyses. Results showed that sex-biased effects were observed in the efficacy of LNS8801 and that LNS8801 shows a UV-protective influence in both male and female TGS mice.

Potential Wound Healing and Anti-Melanogenic Activities in Skin Cells of Aralia elata (Miq.) Seem. Flower Essential Oil and Its Chemical Composition.

Aralia elata (Miq.) Seem. (AES; family Araliaceae) is a medicinal plant and has been reported to have various bioactivities, including anticancer and hepatotoxicity protective activities. However, no studies have investigated the biological activities of AES or its extracts on skin. To address this, we aimed to explore the effect of AES-flower-derived absolute-type essential oil (AESFEO) on skin-related biological activities, especially skin wound healing and whitening-related responses in skin cells (human-derived keratinocytes [HaCaT cells] and melanocytes [B16BL6 cells]) and to identify the components of AESFEO. Cell biological activities were analyzed using WST and BrdU incorporation assays, ELISA, or by immunoblotting. In HaCaT cells, AESFEO promoted proliferation, type IV collagen production, and enhanced the phosphorylations of Erk1/2, p38 MAPK, JNK, and Akt. In B16BL6 cells, AESFEO reduced serum-induced proliferation, α-MSH-stimulated increases in melanin synthesis and tyrosinase activity, and α-MSH-induced increases in MITF, tyrosinase, TRP-1, and TRP-2 expressions. In addition, AESFEO inhibited the phosphorylation of Erk1/2, p38 MAPK, and JNK in α-MSH-stimulated B16BL6 cells. Eighteen compounds were identified in AESFEO by GC/MS. These results suggest that AESFEO has beneficial effects on keratinocyte activities related to skin wound healing and melanocyte activities related to inhibition of skin pigmentation. AESFEO may serve as a useful natural substance for developing agents that facilitate skin wound healing and inhibit melanogenesis.

Decoding the Molecular Mechanisms of BRAF V600E-Induced Nevi Formation.

Melanocytes derived from neural crest cells harbor the BRAF V600E mutation, which is the predominant driver of nevus formation in humans. This mutation leads to malignant cell proliferation and subsequent cell cycle arrest, culminating in oncogene-induced senescence and nevus development. Nevertheless, emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAF V600E-induced senescent melanocytes. Moreover, the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAF V600E, via the mitogen-activated protein kinase signaling pathway, triggers nevus formation. This study provides an overview and discussion of the molecular mechanisms underpinning BRAF V600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation. It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAF V600E animal models created through gene editing technologies.

The Effect of Fractional Carbon Dioxide Laser on Melanogenesis in Human Melanocytes and Vitiligo Mouse Models.

Introduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation. Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content. Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes. Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.

High charge of cerebroid nests in nodular melanomas predicts tumor aggressiveness and high mutational tumoral burden: a pilot study.

Purpose: Even today, melanoma is a highly aggressive neoplasm with a high mortality rate. The nodular type is very aggressive and has cerebroid nests of melanocytes (CNMs) at the growth edge, morphologically similar to the poorly differentiated neoplastic epithelial cell clusters described in colorectal, breast, and endometrioid endometrial cancers. Patients and methods: We selected 25 nodular melanomas (NMs) with known molecular profiles, of which the entire paraffin-embedded lesion was available. We counted CNMs under a microscopic at a magnification of 20x (i.e., a microscopic field with a major axis of 1 mm). Based on the number of CNMs in the area, melanomas were classified into three groups: G1 (CNMs ranging from 0 to 4), G2 (CNMs ranging from 5 to 9), and G3 (CNMs ≥ 10). The presence of CNMs and their counts were compared with molecular and histopathological data. Results: Seventeen (NMs) were grouped as G1 (68%), 5 as G2 (20%), and 3 as G3 (12%) based on CNMs count. The presence of CNMs correlated with epithelioid cell morphology (p < 0.05), Clark IV and V levels (p < 0.05), vascular invasion (p < 0.05), and biological mutants (p < 0.05). Melanomas with ≥ 10 CNMs more frequently show ulceration (p < 0.02) and the BRAF V600E mutation (p < 0.02). Conclusion: CNMs count has a predictive role regardless of tumor size; their association with the BRAF V600E mutation suggests their predictive significance in response to biologics. However, further investigations are needed to strengthen this hypothesis.

Unveiling Oral Malignant Melanoma: Clinicopathological Details of a Case.

Oral malignant melanoma is a rare tumor of the oral cavity. It is more common among Negros and Japanese people. Initial symptoms are frequently overlooked, resulting in a delayed diagnosis and poor prognosis with a 5-year survival rate. Unlike melanomas in other sites, it is uncommon and thus lacks a well-defined classification system and treatment regimen. The survival rate is mainly correlated with early diagnosis and treatment. A 54-year-old male reported to our department with a de novo fast-growing exophytic proliferative pigmented lesion for six months. After proper radiographic analysis, an incisional biopsy was done which revealed the presence of nests and fascicles of pleomorphic spindle cells with hyperchromatic nuclei and abundant brown pigments rendering it a provisional diagnosis of oral malignant melanoma which was later confirmed by immunohistochemistry (IHC). PET-CT scan revealed widespread metastasis. This article stresses the importance of identification of initial symptoms which are frequently overlooked, resulting in a delayed diagnosis and poor prognosis.

Melanocyte lineage dynamics in development, growth and disease.

Melanocytes evolved to produce the melanin that gives colour to our hair, eyes and skin. The melanocyte lineage also gives rise to melanoma, the most lethal form of skin cancer. The melanocyte lineage differentiates from neural crest cells during development, and most melanocytes reside in the skin and hair, where they are replenished by melanocyte stem cells. Because the molecular mechanisms necessary for melanocyte specification, migration, proliferation and differentiation are co-opted during melanoma initiation and progression, studying melanocyte development is directly relevant to human disease. Here, through the lens of advances in cellular omic and genomic technologies, we review the latest findings in melanocyte development and differentiation, and how these developmental pathways become dysregulated in disease.

Exosomal miR-222-3p derived from dermal papilla cells inhibits melanogenesis in melanocytes by targeting SOX10 in rabbits.

Objective: Dermal papilla cells (DPCs) play a pivotal role in hair follicle development and can modulate melanogenesis in melanocytes (MCs) through their microenvironment. Our previous studies have demonstrated that the level of exosomal miR-222-3p derived from DPCs of white Rex rabbits are significantly higher than those of black Rex rabbits. However, the specific role and underlying molecular mechanisms of exosomal miR-222-3p in melanogenesis remain elusive. Methods: DPCs and MCs were isolated from hair follicles of Rex rabbits and identified using western blotting (WB) and immunofluorescent staining. Exosomes derived from DPCs (DPCs-exos) were characterized using nanoparticle tracking analysis, transmission electron microscopy, and WB. To investigate cell-cell crosstalk mediated by exosomes, MCs were co-cultured with CM-Dil-labeled DPCs-exos. The expression of miR-222-3p in skin tissue and exosomes was quantitatively assessed using quantitative real-time PCR (qRT-PCR). The transmission of DPCs-secreted exosomal miR-222-3p to MCs was demonstrated using Cy3-labeled miR-222-3p in conjunction with transwell assays. The impact of miR-222-3p on melanin synthesis was evaluated using the NaOH method, CCK-8, and Annexin V-FITC/PI assays. SOX10, a potential target gene regulated by miR-222-3p, was validated using a dual-luciferase reporter assay, site-specific mutation, and WB. Results: Increased levels of miR-222-3p were observed in the skin and DPCs-exos of white Rex rabbits compared to those of black Rex rabbits. Effective internalization of CM-Dil-labeled DPCs-exos by MCs was observed. Furthermore, exosomal miR-222-3p derived from DPCs was transferred to MCs. Functionally, miR-222-3p significantly inhibited MCs proliferation, induced apoptosis and inhibited melanin synthesis. SOX10 was confirmed as a direct target of miR-222-3p in this regulatory cascade. Conclusion: The findings demonstrate that exosomal miR-222-3p, derived from DPCs, suppresses melanogenesis in MCs by targeting SOX10, thus unveiling a novel mechanism of exosome involvement in melanogenesis.

Revealing the UV response of melanocytes in xeroderma pigmentosum group A using patient-derived induced pluripotent stem cells.

BACKGROUND: Xeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes: MCs) as disease target cells, establishing MCs in primary cultures is challenging. OBJECTIVE: Elucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation. METHODS: iPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12 h after irradiation with 30 or 150 J/m2 of UV-B using microarray analysis. RESULTS: XP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m2 of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150 J/m2 UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30 J/m2 UV exposure. CONCLUSION: We revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP.

The Role of PGC-1α in Aging Skin Barrier Function.

Skin provides a physical and immune barrier to protect the body from foreign substances, microbial invasion, and desiccation. Aging reduces the barrier function of skin and its rate of repair. Aged skin exhibits decreased mitochondrial function and prolonged low-level inflammation that can be seen in other organs with aging. Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), an important transcriptional coactivator, plays a central role in modulating mitochondrial function and antioxidant production. Mitochondrial function and inflammation have been linked to epidermal function, but the mechanisms are unclear. The aim of this review is to discuss the mechanisms by which PGC-1α might exert a positive effect on aged skin barrier function. Initially, we provide an overview of the function of skin under physiological and aging conditions, focusing on the epidermis. We then discuss mitochondrial function, oxidative stress, cellular senescence, and inflamm-aging, the chronic low-level inflammation observed in aging individuals. Finally, we discuss the effects of PGC-1α on mitochondrial function, as well as the regulation and role of PGC-1α in the aging epidermis.

Up-and-Coming Drugs for the Treatment of Vitiligo.

Vitiligo is a chronic autoimmune disease that causes depigmented patches on the skin. It affects 0.5%-2.0% of the global population. It goes beyond physical appearance, often leading to stigmatization, low self-esteem, and depression, burdening patients with psychosocial challenges. The pathogenesis of vitiligo involves the loss of melanocytes due to autoreactive CD8+ T cells, triggered by environmental stressors and exacerbated by cellular vulnerabilities and immune responses. The release of danger signals and pro-inflammatory factors initiates an immune cascade perpetuating melanocyte destruction, mainly driven by interferon-γ and the C-X-C motif chemokine ligand 9/10-chemokine receptor 3 axis. Long-lasting tissue-resident memory T cells (Trms) and cytokines contribute to lesion persistence. Current treatments focus on topical steroids and tacrolimus, systemic steroids, and phototherapies, but their efficacy remains suboptimal, necessitating the development of new therapeutic options. Building on recent advancements in understanding the immunological mechanisms in vitiligo pathogenesis, with the initiation of Food and Drug Administration approval of topical ruxolitinib, various potential treatment options such as JAK inhibitors, cytokine blockers, and Trm or regulatory T cell targeting agents are being clinically researched and anticipated for vitiligo based on both preclinical and clinical data. This review aims to categorize and summarize the diverse investigational drugs currently undergoing clinical trials for vitiligo. By examining clinical outcomes, it is anticipated that this review will bring hope to dermatologists and patients regarding vitiligo, a condition that has historically posed challenges and transform it into a realm of potential possibilities.

Analysis of granulysin expression in vitiligo and halo-nevus.

Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases.

Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes.

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 µg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco's phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.

Transcriptome-wide profiling for melanocytes derived from newborn and adult human epidermis with enhanced proliferation.

The senescence-associated protein p16INK4A acts as a limiter element in cell-cycle progression. The loss of p16INK4A function is causally related to cellular immortalization. The increase in p16INK4A levels with advancing age was demonstrated in melanocytes. However, the characteristic difference between young and senescent melanocytes affecting immortalization of melanocytes remains unclear. In this study, we generated 10 different cell lines in total from newborn (NB) and adult (AD) primary normal human epidermal melanocytes (NHEM) using four different methods, transduction of CDK4R24C and cyclin D1 (K4D), K4D with TERT (K4DT), SV40 T-antigen (SV40T), and HPV16 E6 and E7 (E6/E7) and performed whole transcriptome sequencing analysis (RNA-Seq) to elucidate the differences of genome-wide expression profiles among cell lines. The analysis data revealed distinct differences in expression pattern between cell lines from NB and AD although no distinct biological differences were detected in analyses such as comparison of cell morphology, evaluation of cell proliferation, and cell cycle profiles. This study may provide useful in vitro models to benefit the understanding of skin-related diseases.