Follicular Stem Cells Research Articles

Frontal fibrosing alopecia—A new absolute contraindication for deep chemical peels

Frontal fibrosing alopecia (FFA) is characterized by a receding hairline in the frontotemporal region due to the gradual loss of hair follicles and then follicular stem cells and follicular fibrosis. Follicular stem cells are crucial in skin healing after chemical peeling and other resurfacing procedures. Although there is a possible association of FFA with a history of facial and scalp surgical procedures, there is no information on the safety of cosmetic procedures in patients with FFA. We report five patients with FFA who experienced unusual and complicated outcomes after undergoing a deep chemical peel (phenol and croton oil). As the prevalence of FFA continues to increase globally, it is essential to raise awareness about the potential incompatibility of this dermatologic disorder with specific cosmetic procedures, such as deeper peels and other resurfacing modalities.

Efficacy of Low Level Laser Therapy Combined with Scalp Microneedling using Clobetasol Propionate 0,05% Solution for the Management of Androgenetic Alopecia

Androgenetic alopecia (AGA) is the most common, affecting over half of men and women. Low-level laser therapy (LLLT) has been claimed as a safe devise-based modality for stimulating hair growth in men and women in AGA. LLLT promote hair growth. Although the mechanism is still unclear, it is postulated that this action is due to mitosis acceleration and may be due to the activation of follicular keratinocytes and stem cells. Microneedling is also known as collagen induction therapy. It has been proposed that the trauma generated by needle penetration in the skin induces dermis regeneration. This research aims to assess the effectiveness of LLLT combined with scalp microneedling in the management of AGA. Three adult patients with AGA were subjected to scalp microneedling using clobetasol propionate 0,05% solution plus LLLT for 25 minutes. The treatment was performed at monthly intervals. Results have shown statistically significant improvement after treatment for three months. Low-level laser therapy combined with scalp microneedling could be a safe and good modality for managing AGA as determined by the clinical.

Basic principles of hair follicle structure, morphogenesis, and regeneration.

Diseases affecting the hair follicle are common in domestic animals, but despite the importance of an intact skin barrier and a fully functional hair coat, knowledge about the detailed morphological features and the diversity of these complex mini-organs are often limited, although mandatory to evaluate skin biopsies with a history of alopecia. The factors that regulate the innate hair follicle formation and the postnatal hair cycle are still not completely understood in rodents, only rudimentarily known in humans, and are poorly understood in our companion animals. This review aims to summarize the current knowledge about hair follicle and hair shaft anatomy, the arrangement of hair follicles, hair follicle morphogenesis in the embryo, and the lifelong regeneration during the postnatal hair cycle in domestic animals. The role of follicular stem cells and the need for a multitude of interacting signaling events during hair follicle morphogenesis and regeneration is unquestioned. Because of the lack of state of the art methods that can be applied in rodents but are not feasible in companion animals, most of the information in this review is based on rodent studies. However, the few data from domestic animals that are available will be discussed, and it can be assumed that at least the principal molecular mechanisms are similar in rodents and other species.

Human Ovarian Follicular Fluid Mesenchymal Stem Cells Express Osteogenic Markers When Cultured on Bioglass 58S-Coated Titanium Scaffolds.

Recent studies have reported that stem cells (human follicular fluid mesenchymal stem cells or hFF-MSCs) are present in ovarian follicular fluid (hFF) and that they have a proliferative and differentiative potential which is similar to that of MSCs derived from other adult tissue. These mesenchymal stem cells, isolated from human follicular fluid waste matter discarded after retrieval of oocytes during the IVF process, constitute another, as yet unutilized, source of stem cell materials. There has been little work on the compatibility of these hFF-MSCs with scaffolds useful for bone tissue engineering applications and the aim of this study was to evaluate the osteogenic capacity of hFF-MSCs seeded on bioglass 58S-coated titanium and to provide an assessment of their suitability for bone tissue engineering purposes. Following a chemical and morphological characterization with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), cell viability, morphology and expression of specific osteogenic markers were examined after 7 and 21 days of culture. The hFF-MSCs seeded on bioglass and cultured with osteogenic factors, when compared with those seeded on tissue culture plate or on uncoated titanium, exhibited enhanced cell viability and osteogenic differentiation, as reflected by increased calcium deposition and increased ALP activity with expression and production of bone-related proteins. Taken together, these results demonstrate that MSCs from human follicular fluid waste materials can be easily cultured in titanium scaffolds coated with bioglass, having osteoinductive properties. This process has significant potential for regenerative medicine applications and indicates that hFF-MSCs may be a valid alternative to hBM-MSC cells in experimental models in bone tissue engineering.

Non‐apoptotic caspase activation ensures the homeostasis of ovarian somatic stem cells

Current evidence has associated caspase activation with the regulation of basic cellular functions without causing apoptosis. Malfunction of non‐apoptotic caspase activities may contribute to specific neurological disorders, metabolic diseases, autoimmune conditions and cancers. However, our understanding of non‐apoptotic caspase functions remains limited. Here, we show that non‐apoptotic caspase activation prevents the intracellular accumulation of the Patched receptor in autophagosomes and the subsequent Patched‐dependent induction of autophagy in Drosophila follicular stem cells. These events ultimately sustain Hedgehog signalling and the physiological properties of ovarian somatic stem cells and their progeny under moderate thermal stress. Importantly, our key findings are partially conserved in ovarian somatic cells of human origin. These observations attribute to caspases a pro‐survival role under certain cellular conditions.

Interstitial Cell Dysregulation in Allergic Contact Dermatitis: A Morphodynamic Study of Novel Interstitial Cell Telocytes.

Allergic contact dermatitis (ACD) is an occupation-dependent skin disease that afflicts humans with recurrent, non-specific episodes. Telocyte (TC) is a novel interstitial cell discovered in recent years and, together with fibroblasts, constitutes the predominant interstitial cell population in the skin. The purpose of this study was to investigate the morphodynamic changes of interstitial cells, especially TCs, in the skin during the development and treatment of ACD by histological and microscopic scientific methods. Hematoxylin-eosin staining, Masson staining, immunohistochemistry (IHC), immunofluorescence (IF), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to track morphodynamic changes in interstitial cells during the development and treatment in the ACD-involved skin induced by 2,4-dinitrochlorobenzene (DNCB). The results demonstrated that TCs were mainly present around dermal collagen fibers, perivascular (except dermal papillary vascular loop), and skin appendages, which expressed CD34+, Vimentin+, PDGFR-α+, and α-SMA-. The absence of TCs during ACD development and after ACD recovery causes dermal interstitial cell dysregulation. The special anatomical relationships between TCs, immune cells, and follicular stem cells were also revealed, suggesting their potential dermatitis-regulating function. In a nutshell, our results provide morphodynamic evidence for the process of ACD development and recovery and offer potential cytological ideas for ACD treatment.

Not Follicular but Dermal Melanocyte Precursors Are Histopathologically Retained in Vitiligo

Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF+/Fzd4+ cells in the hair follicle were significantly decreased in number in the lesions, Nestin+ and p75NGFR+ cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.

Aging in the sebaceous gland.

Sebaceous glands (SGs) originate from hair follicular stem cells and secrete lipids to lubricate the skin. The coordinated effects of intrinsic and extrinsic aging factors generate degradation of SGs at a late age. Senescence of SGs could be a mirror of the late aging of both the human body and skin. The procedure of SG aging goes over an initial SG hyperplasia at light-exposed skin areas to end with SG atrophy, decreased sebum secretion, and altered sebum composition, which is related to skin dryness, lack of brightness, xerosis, roughness, desquamation, and pruritus. During differentiation and aging of SGs, many signaling pathways, such as Wnt/β-catenin, c-Myc, aryl hydrocarbon receptor (AhR), and p53 pathways, are involved. Random processes lead to random cell and DNA damage due to the production of free radicals during the lifespan and neuroendocrine system alterations. Extrinsic factors include sunlight exposure (photoaging), environmental pollution, and cigarette smoking, which can directly activate signaling pathways, such as Wnt/β-catenin, Notch, AhR, and p53 pathways, and are probably associated with the de-differentiation and hyperplasia of SGs, or indirectly activate the abovementioned signaling pathways by elevating the inflammation level. The production of ROS during intrinsic SG aging is less, the signaling pathways are activated slowly and mildly, and sebocytes are still differentiated, yet terminal differentiation is not completed. With extrinsic factors, relevant signaling pathways are activated rapidly and fiercely, thus inhibiting the differentiation of progenitor sebocytes and even inducing the differentiation of progenitor sebocytes into keratinocytes. The management of SG aging is also mentioned.

Adnexal squamous cell carcinoma: incidence of eyelid margin involvement

ABSTRACT Purpose We aimed to perform a review of facial and periorbital squamous cell carcinoma (SCC) cases to assess the relative incidence of eyelid margin involvement. Methods This is a retrospective review of all patients with biopsy-proven SCC who were evaluated at a single oculoplastic surgery practice from 2007 to 2019. The charts were reviewed for the anatomical location of the malignancy, and those involving the eyelid were further divided into marginal and non-marginal lesions. Statistical analysis was performed using a one proportion z-test Results A total of 76 patients with a diagnosis of biopsy-proven periorbital and facial SCC were identified, 67 involved the ocular adnexa. Thirty-nine (58.2%) patients had lesions located on the eyelid. Of these, 33 (84.6% p < 0.0001, 95% CI 69.45–94.13) had lesions located at the margin, six of the 39 lesions were non-marginal. The remaining lesions were present within the brow (n = 10, 14.9%), medial canthus (n = 10, 14.9%), palpebral conjunctiva (n = 1, 1.5%), or orbit (n = 1, 1.5%). In six patients (8.9%) lesions involved multiple anatomic subunits. Conclusion We present our investigation of the incidence of SCC of the marginal vs. non-marginal eyelid, revealing a statistically significant increased involvement of the eyelid margin. Future investigations are necessary to further elucidate the vulnerability of the eyelid margin to the development of SCC in particular in regards to the role of the unique genetic expression profile of eyelash follicular stem cells.

Drugs targeting epithelial-mesenchymal transition molecules for treatment of lichen planopilaris.

Primary cicatricial alopecia (PCA), also known as scarring alopecia, comprises a diverse group of hair disorders that cause permanent destruction of the pilosebaceous unit, resulting in disappearance of the follicular ostia. Lichen planopilaris (LPP) is a subtype of primary lymphocytic cicatricial alopecia. There is an urgent need to identify novel molecules that successfully target specific pathogenic pathways in LPP to inhibit and reverse disease progression. Recent studies into LPP pathogenesis have discovered that follicular stem cells undergo epithelial-mesenchymal transition (EMT). We sought to identify drugs that target molecules involved in EMT to repurpose these drugs for treatment of LPP. We identified 8 molecules and 15 drugs that target these EMT molecules. Only four of these drugs (pioglitazone, tofacitinib, barcitinib and apremilast) have been reported in individual cases or case series of patients with LPP and controlled studies are missing. We describe each drug and mechanism of action target EMT in detail. Although previous studies have demonstrated the efficacy of EMT inhibitors in anticancer therapy, there are, to our knowledge, no studies using EMT-attenuating drugs for the treatment of LPP. The treatment molecules discussed in this paper provide a new platform for clinical studies and controlled trials in LPP.

Epithelial-Mesenchymal Interaction in Hair Regeneration and Skin Wound Healing.

Interactions between epithelial and mesenchymal cells influence hair follicles (HFs) during embryonic development and skin regeneration following injury. Exchanging soluble molecules, altering key pathways, and extracellular matrix signal transduction are all part of the interplay between epithelial and mesenchymal cells. In brief, the mesenchyme contains dermal papilla cells, while the hair matrix cells and outer root sheath represent the epithelial cells. This study summarizes typical epithelial–mesenchymal signaling molecules and extracellular components under the control of follicular stem cells, aiming to broaden our current understanding of epithelial–mesenchymal interaction mechanisms in HF regeneration and skin wound healing.

Protective Effect of Hydroxygenkwanin against Hair Graying Induced by X-Ray Irradiation and Repetitive Plucking

Hair graying in mice is caused by various injuries such as X-ray radiation and repeated plucking that ultimately damage melanocytes and their stem cells (melanocyte stem cells). In X-ray‒induced hair graying, injuries first manifest as a loss-of-niche function of hair follicular keratinocyte stem cells to maintain melanocyte stem cells. Thus, we hypothesized that hair follicular keratinocyte stem cells could be a practical target to prevent hair graying. In this study, we investigated the in vivo effect of the flavonoid hydroxygenkwanin, which has been shown to exert the best protection on human epidermal keratinocytes against in vitro X-ray‒induced cytological effects, using X-ray‒induced and repeated hair plucking‒induced hair graying mice models. We found that hydroxygenkwanin exerted a remarkable effect in preventing hair graying; however, when receptor Y kinase Kit-mutant mice were used, no prevention effect was observed. Therefore, we propose that Kit signaling might be involved in the hydroxygenkwanin-induced protective effect against hair graying.

Management of Coccygeal Radiation-Induced Ulcer Using Injectable Acellular Dermal Matrix Combined with Negative Pressure Wound Therapy: A Case Report

Radiation ulcers can occur as a complication following exposure to ionizing radiation. Advances in medical technology, followed by the wider range of radiation application in recent decades has steadily increased the incidence of radiation ulcers. Radiation causes hypoxia, hypovascularity, and hypocellularity in tissues. Moreover, the surrounding skin adjacent to the radiation ulcer lacks follicular stem cells and is more prone to chronic, non-healing wounds. While no guidelines have been established regarding optimal treatment, management facilitating angiogenesis and migration of fibrogenic cells can be a recommended option, considering the etiology of ulcers induced by radiation exposure. Herein, we present a patient exposed to prolonged radiation during a fluoroscopic intervention procedure, who had developed a vast radiation ulcer at his coccyx, and was completely treated with injectable acellular dermal matrix combined with 14 weeks of negative pressure wound therapy.

Augmenting Peripheral Nerve Regeneration Using Hair Follicle Stem Cells in Rats.

Cell therapy is the most advanced treatment of peripheral nerve injury. This study aimed to determine the effects of transplantation of hair follicle stem cells on the regeneration of the sciatic nerve injury in rats. The bulge region of the rat whisker were isolated and cultured. Morphological and biological features of the cultured bulge cells were observed by light microscopy and immunocytochemistry methods. Percentages of CD34, K15, and nestin cell markers expression were demonstrated by flow cytometry. Rats were randomly divided into 3 groups of injury, epineurium, and epineurium with cells in which rat Hair Follicular Stem Cells (rHFSCs) were injected into the site of the nerve cut. HFSCs were labeled with Bromodeoxyuridine (BrdU), and double-labeling immunofluorescence was performed to study the survival and differentiation of the grafted cells. After 8 weeks, electrophysiological, histological, and immunocytochemical analysis assessments were performed. Rat hair follicle stem cells are suitable for cell culture, proliferation, and differentiation. The results suggest that transplantation of rat hair follicle stem cells can regenerate sciatic nerve injury; moreover, electrophysiology and histology examinations show that sciatic nerve repair was more effective in the epineurium with cell group than in the other experimental group (P<0.05). The achieved results propose that hair follicle stem cells improve axonal growth and functional recovery after peripheral nerve injury. This study showed that rat hair follicle stem cells are suitable for cell culture, proliferation and differentiationThe results suggested that transplantation of rat hair follicle stem cells had the potential capability of regenerating sciatic nerve injuryEvidence of electrophysiology and histology showed Concomitant use of epineurium with hair follicle stem cell was more effective repairment. Although repairing damaged peripheral nerves has always been a medical challenge, but peripheral nerve injury has been successfully repaired using various procedures such as nerve auto-graft or stem cell therapy. The functional reconstruction is the most important after therapy because of that primary nerve repair or use of nerve autograft, are still accepted as golden standard methods for treatment. Considerable recent interest has been focused on adult stem cells for both research and clinical applications. A highly promising source of relatively abundant and accessible, active, multipotent adult stem cells are obtained from hair follicles. In research the hair follicle stem cells implanted into the gap region of a severed sciatic nerve injury greatly enhanced the rate of nerve regeneration and the restoration of nerve function. Time is one of the several aspects require specific attention in the clinical treatment of peripheral nerve injury. Because delay of nerve injury treatment may cause neurobiological alterations in neurons and Schwann cells, impairing nerve functional recovery and affect neuron survival. In this study, concluded that stem cell injection 2 weeks after injury in the damaged nerve epineurium repairs nerve fibers, while electrophysiology of the leg muscles showed that muscle function was significantly improved. It indicates the repair of muscular innervation and nerve repair. The results pave the way for further research on this topic.

Primary cicatricial alopecia: Recent advances in evaluation and diagnosis based on trichoscopic and histopathological observation, including overlapping and specific features.

Primary cicatricial alopecia (PCA) is a form of alopecia in which inflammatory cells target follicles, including the bulge region containing follicular stem cells, leading to permanent alopecia. New classifications of PCA subtypes have recently been proposed, including those that account for novel trichoscopic and histopathological features of PCA, enabling greater precision in the evaluation and diagnosis of this condition. Nonetheless, diagnosis remains challenging clinically and histopathologically because the etiology of PCA is multifactorial. Inconsistent use of terminology, overlapping disease concepts, and changes in the clinical or histopathological severity of inflammation in the disease course in the same patient also make diagnosis quite challenging. The present study comprehensively reviews recent progress in diagnostic techniques, including the use of clinical, trichoscopic, and histopathological features, in evaluating each PCA subtype, containing overlapping and specific features. Elucidating the features of PCA, including those that are common to multiple subtypes as well as specific to each in both early and advanced-stage lesions, is important for accurate diagnosis. Improving the evaluation and treatment of this disease depends on having a broader clinical understanding that takes into account not only the features of the disease at a given point in time, but also the changes that occur during the entire disease course.

Chronic metabolic and induced stress impacts mesenchymal stromal cell differentiation and modulation of dental origin in-vitro

The impact of induced (smoking) and metabolic stress (diabetes) on dental stem cells with respect to pre-impact consideration on differentiation and bone formation were investigated. The progenitor stem cells isolated from dental pulp, follicle and gingival tissues were phenotyped and subjected to nicotine and high glucose stress mimicking the smoking and diabetic condition in-vitro. The results showed that the cellular viability post treatment with 100 µM nicotine and 10uM glucose was about 86% to 89% respectively in all the three cell types while about 73% in combined nicotine and glucose treatment. No variation in the expression of pro-inflammatory TNF-α, IL-1β and IL-12 in all the three cell types were noticed. The observed viability in nicotine treated cells were due to elevated IL-6, IL-10 while in glucose was due to brain derived neurotropic factor (BDNF). Higher expression of IL-4, IL-6, IL-10, TGF-β and heme oxygenase −1 (HO-1) were found high in both stressors treated cells. Differentiation and mineralization markers Alkaline phosphatase (ALP), Collagenase I (COL1), Osteocalcin, Runt related transcription factor 2 (RUNX2), Osteopontin and Bone sialoprotein were expressed in the dental pulp stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) at varying levels post nicotine or glucose treatment while not significantly observed in dental follicular stem cells (DFSCs). Therefore, it is evident that the stem cells of varied dental origin responded to the stress are more or less uniform with physiological delay in differentiation into osteoblast. It is evident from the study that, the metabolic or induced stress subverts the process of regenerative healing by mesenchymal stromal cells with their anatomical niche.

Differences in anatomical area-specific wound healing in hidradenitis suppurativa/acne inversa after surgery

Hidradenitis suppurativa/acne inversa is an inflammatory, debilitating disease for which wide local excision of the affected area with secondary wound healing is considered the treatment of first choice for the inactive scarring form or after adequate anti-inflammatory medical treatment. In this study, we aimed to assess the duration of complete secondary wound healing after surgical intervention for hidradenitis suppurativa/acne inversa. Twenty-three surgical procedures in 17 consecutive patients (eight female, nine male) were evaluated for duration of secondary wound healing at axillary or anogenital/inguinal sites. To investigate the contribution of hair follicle bulge progenitor cells in wound re-epithelialization, tissue samples of lesional and perilesional skin were analysed for expression of the stem cell marker, cytokeratin 15 (CK15), and CD200, a marker for human follicular stem cells that resides in the bulge area. Initial wound size did not differ significantly between surgical wounds in the axillary (mean: 30.0 cm2 ± 5.4) and anogenital/inguinal (mean: 35.3 cm2 ± 5.7) region. However, healing time to complete wound closure was almost twice as fast in the anogenital/inguinal (mean: 132 days ± 10.4) than axilla area (mean: 254 days ± 39.1; p < 0.01). The accelerated wound healing in the anogenital/inguinal region was accompanied by significantly enhanced CK15 and CD200 expression, compared to axillary wounds (p < 0.05). The anogenital/inguinal region showed significantly faster secondary wound healing after surgical intervention for hidradenitis suppurativa/acne inversa compared to axillary wounds. We suspect differences in pilosebaceous unit density and thus hair follicle progenitor cells (as mirrored by CK15 and CD200 expression) to be the main driver behind this finding.

Eruptive Necrotizing Infundibular Crystalline Folliculitis: An Expression of an Abortive Sebaceous Follicular Repair Pathway Linked to Committed Infundibular Stem Cells?

:Necrotizing infundibular crystalline folliculitis is a rare entity, which is a distinctive clinical and histopathological entity. Eruptive yellow waxy umbilicated folliculocentric plugs clinically correspond to pale crystalline filaments embedded in an amorphous sebum-rich material. Remarkably, only the superficial infundibular ostia remain, and the distended cavity is devoid of a follicular or sebaceous gland remnant. The pathogenesis of this enigmatic event remains to be established. The emergence of necrotizing infundibular crystalline folliculitis (NICF) as a paradoxical side effect of antitumor inhibitors epidermal growth factor receptor vascular endothelial growth factor and more recently programmed death-1 represents the expression of altered molecular pathways that underpin the pathogenesis of NICF. To explore these pathways, it is necessary to explore the hierarchy of follicular stem cells, particularly the potential role of committed infundibular stem cells that play a key role in wound healing. Committed infundibular stem cells are closely linked to the sebaceous gland stem cell axis, and this has relevance in the process of homeostatic repair of sebaceous follicles in the wake of folliculitis. The unscheduled modulation of this infundibular homeostatic sebaceous repair axis by epidermal growth factor receptor vascular endothelial growth factor, and programmed death-1 may lead to an aberrant outcome with metaplasia of infundibular keratinocytes to sebocytes. In the absence of sebaceous gland differentiation, these metaplastic infundibular sebocyte cells would lead to the consumption and loss of the infundibulum as a result of holocrine sebum production. This conceptual pathogenic pathway for NICF is constructed by incorporating recent advances in the fields of follicular stem cells, wound repair, follicular homeostasis, regulatory T cells, and molecular pathways linked to the biologicals inducing NICF.

A novel mouse model to evaluate neuropeptide Y-mediated melanocyte pathology.

Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo aetiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY overexpression induces progressive hair greying (depigmentation) due to premature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.

Defining microRNA signatures of hair follicular stem and progenitor cells in healthy and androgenic alopecia patients

BackgroundThe exact pathogenic mechanism causes hair miniaturization during androgenic alopecia (AGA) has not been delineated. Recent evidence has shown a role for non-coding regulatory RNAs, such as microRNAs (miRNAs), in skin and hair disease. There is no reported information about the role of miRNAs in hair epithelial cells of AGA. ObjectivesTo investigate the roles of miRNAs affecting AGA in normal and patient’s epithelial hair cells. MethodsNormal follicular stem and progenitor cells, as well as follicular patient’s stem cells, were sorted from hair follicles, and a miRNA q-PCR profiling to compare the expression of 748 miRNA (miRs) in sorted cells were performed. Further, we examined the putative functional implication of the most differentially regulated miRNA (miR-324-3p) in differentiation, proliferation and migration of cultured keratinocytes by qRT-PCR, immunofluorescence, and scratch assay. To explore the mechanisms underlying the effects of miR-324-3p, we used specific chemical inhibitors targeting pathways influenced by miR-324-3p. ResultWe provide a comprehensive assessment of the "miRNome" of normal and AGA follicular stem and progenitor cells. Differentially regulated miRNA signatures highlight several miRNA candidates including miRNA-324-3p as mis regulated in patient’s stem cells. We find that miR-324-3p promotes differentiation and migration of cultured keratinocytes likely through the regulation of mitogen-activated protein kinase (MAPK) and transforming growth factor (TGF)-β signaling. Importantly, pharmacological inhibition of the TGF-β signaling pathway using Alk5i promotes hair shaft elongation in an organ-culture system. ConclusionTogether, we offer a platform for understanding miRNA dynamic regulation in follicular stem and progenitor cells in baldness and highlight miR-324-3p as a promising target for its treatment.