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1.
Arch Dermatol Res ; 316(6): 330, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38837051

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary cicatricial alopecia that cause a major impact on quality of life due to irreversible hair loss and symptoms as itching, burning and pain. They are characterized by permanent loss of hair follicle stem cells (HFSCs) by pathomechanisms still poorly understood, resulting in poor efficacy of currently available treatments. Caveolae are flask-shaped lipid rafts invaginated within the plasma membrane of multiple cell types. Although their role in the HF physiology and pathophysiology is relatively unknown, we have previously demonstrated that the primary structural component of caveolae (caveolin-1 or Cav1) is upregulated in FFA. Thus, we propose to investigate the expression and localization of caveolae-associated structural proteins (Cav1, Cav2, and Cavin-1) and HFSCs (identified by K15) in both LPP and FFA. We analyzed 4 patients with LPP biopsied in affected and non-affected (NA) scalp, 4 patients with FFA biopsied in affected scalp and 4 healthy controls. Affected scalp of LPP and FFA demonstrated increased levels of Cav1 and Cavin-1 compared with HC and LPP-NA. Moreover, Cav1, Cav2 and Cavin1 all exhibit high colocalization with K15 and their expression appears to be negatively correlated, supporting the hypothesis that these proteins are important players in LPP/FFA and may serve as therapeutic targets in future treatments.


Alopecia , Caveolae , Caveolin 1 , Hair Follicle , Lichen Planus , Up-Regulation , Humans , Alopecia/pathology , Alopecia/metabolism , Hair Follicle/pathology , Hair Follicle/metabolism , Lichen Planus/metabolism , Lichen Planus/pathology , Middle Aged , Female , Caveolin 1/metabolism , Male , Caveolae/metabolism , Scalp/pathology , Adult , Keratin-15/metabolism , Aged , Biopsy , Fibrosis , Stem Cells/metabolism , Stem Cells/pathology , RNA-Binding Proteins/metabolism
2.
J Dermatol ; 51(5): 621-631, 2024 May.
Article En | MEDLINE | ID: mdl-38605467

Alopecia areata refers to an autoimmune illness indicated by persistent inflammation. The key requirement for alopecia areata occurrence is the disruption of immune-privileged regions within the hair follicles. Recent research has indicated that neuropeptides play a role in the damage to hair follicles by triggering neurogenic inflammation, stimulating mast cells ambient the follicles, and promoting apoptotic processes in keratinocytes. However, the exact pathogenesis of alopecia areata requires further investigation. Recently, there has been an increasing focus on understanding the mechanisms of immune diseases resulting from the interplay between the nervous and the immune system. Neurogenic inflammation due to neuroimmune disorders of the skin system may disrupt the inflammatory microenvironment of the hair follicle, which plays a crucial part in the progression of alopecia areata.


Alopecia Areata , Hair Follicle , Neurogenic Inflammation , Alopecia Areata/immunology , Alopecia Areata/etiology , Alopecia Areata/pathology , Humans , Hair Follicle/immunology , Hair Follicle/pathology , Neurogenic Inflammation/immunology , Neurogenic Inflammation/etiology , Neuropeptides/metabolism , Neuropeptides/immunology , Mast Cells/immunology , Keratinocytes/immunology , Keratinocytes/pathology , Apoptosis/immunology , Animals
3.
J Cutan Pathol ; 51(6): 459-467, 2024 Jun.
Article En | MEDLINE | ID: mdl-38443749

BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. METHODS: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. RESULTS: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11-85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow-up duration. Clinically, patients often exhibited symmetric ill-defined patches/plaques involving intertriginous regions with tan-yellow hyperpigmentation and follicular-based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow-up. T-cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small-medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). CONCLUSIONS: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia.


Mycosis Fungoides , Skin Neoplasms , Humans , Mycosis Fungoides/pathology , Mycosis Fungoides/diagnosis , Male , Female , Middle Aged , Adult , Aged , Skin Neoplasms/pathology , Retrospective Studies , Aged, 80 and over , Adolescent , Child , Hair Follicle/pathology
4.
Australas J Dermatol ; 65(4): 311-318, 2024 Jun.
Article En | MEDLINE | ID: mdl-38419202

BACKGROUND: Atrophic acne scarring is a common sequela of inflammatory acne, causing significant problems for affected patients. Although prolonged inflammation and subsequent aberrant tissue regeneration are considered the underlying pathogenesis, the role of epidermal stem cells, which are crucial to the regeneration of pilosebaceous units, remains unknown. OBJECTIVES: To examine the changes occurring in epidermal stem cells in atrophic acne scars. METHODS: Changes in collagen, elastic fibre and human leukocyte antigen (HLA)-DR expression were analysed in normal skin and inflammatory acne lesions at days 1, 3 and 7 after development. The expression of epidermal stem cell markers and proliferation markers was compared between normal skin and mature atrophic acne scar tissue. RESULTS: In acne lesions, inflammation had invaded into pilosebaceous units over time. Their normal structure had been destructed and replaced with a reduced amount of collagen and elastic fibre. Expression of stem cell markers including CD34, p63, leucine-rich repeat-containing G protein-coupled receptor (LGR)6 and LGR5, which are expressed in the interfollicular epidermis, isthmus and bulge of hair follicles, significantly decreased in atrophic acne scar tissue compared to normal skin. Epidermal proliferation was significantly reduced in scar tissue. CONCLUSIONS: These findings suggest that as inflammatory acne lesions progress, inflammation gradually infiltrates the pilosebaceous unit and affects the resident stem cells. This disruption impedes the normal regeneration of the interfollicular epidermis and adnexal structures, resulting in atrophic acne scars.


Acne Vulgaris , Cicatrix , Hair Follicle , Stem Cells , Humans , Acne Vulgaris/complications , Acne Vulgaris/pathology , Cicatrix/pathology , Cicatrix/etiology , Stem Cells/metabolism , Stem Cells/pathology , Hair Follicle/pathology , Atrophy , Collagen/metabolism , Elastic Tissue/pathology , Male , Female , HLA-DR Antigens/metabolism , Cell Proliferation , Young Adult , Adult , Epidermal Cells/metabolism , Epidermis/pathology , Epidermis/metabolism
5.
J Cosmet Dermatol ; 23(5): 1828-1839, 2024 May.
Article En | MEDLINE | ID: mdl-38189587

BACKGROUND: Despite similarities in progressive miniaturization of hair follicles and transition of terminal hairs to vellus hairs, insufficient trichoscopic comparisons between male androgenetic alopecia (MAGA) and female pattern hair loss (FPHL) hinder our ability to select effective treatments. AIM: Our study aimed to explore gender-specific trichoscopic characteristics of MAGA and FPHL, while formulating hypotheses regarding the progression of these conditions across clinical stages. METHODS: We classified 126 male MAGA subjects using Hamilton-Norwood Classification and 57 FPHL subjects using adopted Sinclair Scale. Subsequently, we analyzed nine trichoscopic factors divided into three categories: hair-diameter related, hair-number per follicular unit related, and hair density related factors. RESULTS: Of the nine quantitative trichoscopic factors, hair-diameter and hair-number per follicular unit showed strong correlations with clinical stages in both genders. Hair density, a common trichoscopic factor for hair loss evaluation, weakly correlated with clinical stages in FPHL, but not at all in MAGA. In addition, MAGA was characterized by a progressive reduction in hair-diameter, followed by a reduction in hair-number per follicular unit. FPHL, on the contrary, showed the opposite progression. CONCLUSIONS: Trichoscopic factors vary with disease severity in a gender-specific manner. Our research highlights that MAGA and FPHL involve two distinct streams: hair-diameter decreasing by hair follicle miniaturization (Stream 1), and hair-number per follicular unit decreasing by hair follicle tri-lineage niche dysfunction (Stream 2). MAGA typically starts from Stream 1 to Stream 2, while FPHL starts from Stream 2. These diverse progression pathways underscore the importance of personalized treatment approaches.


Alopecia , Dermoscopy , Disease Progression , Hair Follicle , Hair , Humans , Alopecia/pathology , Male , Female , Adult , Hair Follicle/pathology , Middle Aged , Severity of Illness Index , Young Adult , Sex Factors
6.
Vet Dermatol ; 35(3): 354-359, 2024 Jun.
Article En | MEDLINE | ID: mdl-38247380

Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis have been reported in six female Labrador retrievers from North America. This is the first report of the disease outside North America, describing the clinical and histopathological diagnosis and dermoscopic aspect of the verrucous plaques, treatment and co-morbidities in a female Labrador retriever dog.


La folliculite et la dermatite murale infundibulaire proliférative, lymphocytaire ont été rapportées chez six Labrador retrievers femelles d'Amérique du Nord. Il s'agit du premier rapport de cette affection en dehors de l'Amérique du Nord, décrivant le diagnostic clinique et histopathologique, l'aspect dermatoscopique des plaques verruqueuses, le traitement et les comorbidités chez une femelle Labrador retriever.


A foliculite e dermatite mural linfocítica infundibular proliferativa tem sido relatada em seis cadelas Labrador retriever da América do Norte. Este é o primeiro relato da doença fora da América do Norte, descrevendo o diagnóstico clínico e histopatológico e o aspecto dermoscópico de placas verrucosas, tratamento de comorbidades em uma cadela Labrador retriever.


Se ha publicado la descripción de una foliculitis y dermatitis mural infundibular, linfocítica y proliferativa en seis hembras de Labrador Retriever de América del Norte. Este es el primer informe de la enfermedad fuera de América del Norte, que describe el diagnóstico clínico e histopatológico y el aspecto dermatoscópico de las placas verrugosas, el tratamiento y las comorbilidades en una perra Labrador Retriever.


Dermatitis , Dog Diseases , Folliculitis , Animals , Dogs , Folliculitis/veterinary , Folliculitis/pathology , Dog Diseases/pathology , Female , Dermatitis/veterinary , Dermatitis/pathology , Dermoscopy/veterinary , Apoptosis , Hair Follicle/pathology
7.
J Cosmet Dermatol ; 23(2): 585-590, 2024 Feb.
Article En | MEDLINE | ID: mdl-37735949

OBJECTIVE: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of secondary scarring alopecia caused by infections, and to evaluate its effectiveness. METHODS: A retrospective observational study has been conducted, which included nine patients with secondary scarring alopecia caused by infections. All patients underwent initial autologous FUE hair transplantation surgery, and the occurrence of postoperative complications was monitored. Patient satisfaction was evaluated after 12 months post-surgery. RESULTS: At the follow-up, postoperative satisfaction was 88.9% in nine patients, with only one case of postoperative infection and no incidence of skin necrosis, significant bruising and swelling, unnatural appearance or temporary hair loss. CONCLUSIONS: Autologous FUE hair transplantation is an effective method for treating secondary scarring alopecia caused by infections. This procedure is minimally invasive, resulting in high patient satisfaction and minimal complications postoperatively.


Cicatrix , Hair Follicle , Humans , Alopecia/surgery , Alopecia/complications , Cicatrix/etiology , Cicatrix/surgery , Hair Follicle/pathology , Postoperative Complications/etiology , Postoperative Complications/surgery , Skin Transplantation/methods , Transplantation, Autologous/adverse effects , Retrospective Studies
8.
Vet Dermatol ; 35(2): 126-137, 2024 Apr.
Article En | MEDLINE | ID: mdl-37867253

BACKGROUND: A combination of dermoscopic and histological findings may provide useful information for the diagnosis of hair follicle diseases. However, there are no studies on dermoscopic-histopathological correlations in dogs affected by alopecia X, and comparison of longitudinal versus transversal sectioning of skin biopsy specimens in the assessment of this hair loss disorder has not been thoroughly investigated. HYPOTHESIS/OBJECTIVES: The aim of this study was to correlate dermoscopic and histological features using both longitudinal and transversal sectioning of skin biopsy samples to gain additional information for the diagnosis of alopecia X. ANIMALS: Nineteen Pomeranian dogs affected by alopecia X and five healthy Pomeranians as controls. MATERIALS AND METHODS: Dermoscopic-histological correlation was performed within the diseased group, whereas histological comparisons against controls. The demographic and clinical characteristics also were related to the histological findings. RESULTS: The dermoscopic findings revealed scattered, thinned, short hairs mixed with amorphous keratoseborrhoeic-like material (follicular plugging), perifollicular and intrafollicular scaling, and hyperpigmentation varying from pinpoint black spots to a diffuse texture. Dermoscopic findings correlated with histological findings for selected qualitative and quantitative findings. The usefulness of transversal sections was demonstrated in accurately determining the hair follicular density and counts, growth arrest phases and in identifying mineralisation of hair follicle basement membrane when compared to the longitudinal. Conversely, no correlations between histological findings and demographic and clinical characteristics were detected. CONCLUSIONS AND CLINICAL RELEVANCE: These data provide evidence of the usefulness of dermoscopic evaluation as an accessory diagnostic tool and of transversal sections of skin biopsies as complementary to the diagnosis of alopecia X.


Alopecia , Darier Disease , Animals , Dogs , Alopecia/diagnosis , Alopecia/veterinary , Alopecia/pathology , Hair/pathology , Hair Follicle/diagnostic imaging , Hair Follicle/pathology , Skin/pathology , Darier Disease/pathology , Darier Disease/veterinary
9.
Int J Dermatol ; 63(5): 618-623, 2024 May.
Article En | MEDLINE | ID: mdl-38159030

BACKGROUND: Lonely hair sign is considered as a clue to the diagnosis of frontal fibrosing alopecia (FFA). OBJECTIVE: To report an undescribed variant of alopecia areata (AA) with which the patient developed single hairs and other features similar to FFA and to determine the underlying mechanism. METHODS: We conducted a prospective observational study in patients who presented with receding hairline and single hairs, evaluating the clinical, trichoscopic, and histological features and their correlation. Immunochemistry studies were performed to describe the microenvironment. RESULTS: Eighteen patients were enrolled in the study. Despite the similarity to FFA clinically, these patients showed different histopathology which revealed a normal number of pilosebaceous units, one anagen hair in one or more pilosebaceous units, and others in telogen stage, consistent with single hairs under the naked eye or under trichoscopy. The severity of the hair loss assessed by SALT was no more than 50, but the response to conventional therapy was poor. CONCLUSIONS: This study reports a unique variant of AA. The pathological basis is an increase in the telogen hair follicles, with one anagen hair in one or more pilosebaceous units. Minimal inflammation consisting of CD3+ T lymphocytes and mast cells was demonstrated in the microenvironment.


Alopecia Areata , Fibrosis , Hair Follicle , Hair , Humans , Alopecia Areata/pathology , Alopecia Areata/diagnosis , Alopecia Areata/drug therapy , Prospective Studies , Female , Adult , Male , Middle Aged , Hair Follicle/pathology , Hair/pathology , Young Adult , Mast Cells/pathology , Dermoscopy , Alopecia/pathology , Alopecia/diagnosis , Adolescent , Diagnosis, Differential , T-Lymphocytes/pathology , Severity of Illness Index
11.
J Am Acad Dermatol ; 90(1): 122-124, 2024 Jan.
Article En | MEDLINE | ID: mdl-37364614

BACKGROUND: Proliferating pilar tumors (PPTs) are rare cutaneous neoplasms arising from hair follicles that have both malignant and metastatic potential. OBJECTIVE: To present a systematic review of the epidemiology, clinical characteristics, and treatment and outcome data on PPTs. METHODS: Using the OVID platform, MEDLINE and Embase were searched from inception until May 26, 2022. All studies that provided original data on PPTs in English were included. References of these studies were also cross-checked to identify any additional relevant articles. Oxford's Levels of Evidence-Based Medicine was used for quality assessment. RESULTS: A total of 114 articles, providing data on 361 cases of PPTs, were included in our synthesis. Every study included was either a case series or case report. The mean age at diagnosis was 61.7. Most patients in the synthesis were female (71%), and the majority of cases occurred on the scalp (73.1%). The presence or absence of cytological atypia was only reported in one-third of the cases; 36.8% of cases were classified as malignant and 7.5% metastasized. Although no lesions treated with Mohs micrographic surgery required adjuvant radiation and only one reported recurrence occurred after Mohs surgery, there is insufficient data to make conclusions on a superior treatment modality. LIMITATIONS: All studies in this review were either case reports or case series. CONCLUSIONS AND RELEVANCE: Our study supports the notion that PPTs occur most commonly on the scalp of elderly female patients. Moreover, our findings confirm that PPT is capable of demonstrating aggressive biology and metastasis. Given the lack of uniformity in histologic description, pathologists should be encouraged to comment on the presence and degree of cytological atypia when reporting cases of rare neoplasms such as the PPT. Greater consensus on diagnosis and classification as well as more robust data is needed regarding optimal management.


Hair Diseases , Neoplasms, Adnexal and Skin Appendage , Skin Neoplasms , Aged , Female , Humans , Male , Hair Diseases/pathology , Hair Follicle/pathology , Radiotherapy, Adjuvant , Skin Neoplasms/epidemiology , Skin Neoplasms/therapy , Skin Neoplasms/pathology
12.
Int J Mol Sci ; 24(24)2023 Dec 18.
Article En | MEDLINE | ID: mdl-38139460

Alopecia areata is an autoimmune disease characterized by the immune system attacking self hair follicles, mainly in the scalp. There is no complete cure, and the pathogenesis is still not fully understood. Here, sequencing of skin tissues collected from 1-month-old coarse- and fine-wool lambs identified miR-199a-3p as the only small RNA significantly overexpressed in the fine-wool group, suggesting a role in hair follicle development. MiR-199a-3p expression was concentrated in the dermal papillae cells of sheep hair follicles, along with enhanced ß-catenin expression and the inhibition of PTPRF protein expression. We also successfully constructed a mouse model of alopecia areata by intracutaneous injection with an miR-199a-3p antagomir. Injection of the miR-199a-3p agomir resulted in hair growth and earlier anagen entry. Conversely, local injection with the miR-199a-3p antagomir resulted in suppressed hair growth at the injection site, upregulation of immune system-related genes, and downregulation of hair follicle development-related genes. In vivo and in vitro analyses demonstrated that miR-199a-3p regulates hair follicle development through the PTPRF/ß-catenin axis. In conclusion, a mouse model of alopecia areata was successfully established by downregulation of a small RNA, suggesting the potential value of miR-199a-3p in the study of alopecia diseases. The regulatory role of miR-199a-3p in the PTPRF/ß-catenin axis was confirmed, further demonstrating the link between alopecia areata and the Wnt-signaling pathway.


Alopecia Areata , MicroRNAs , Animals , Mice , Antagomirs , beta Catenin/genetics , Disease Models, Animal , Hair Follicle/pathology , MicroRNAs/genetics , Sheep
13.
J Pak Med Assoc ; 73(11): 2260-2262, 2023 Nov.
Article En | MEDLINE | ID: mdl-38013542

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides characterized by infiltration of hair follicle epithelium by neoplastic lymphoid cells. Generally, it is usually typified by indurated plaques and tumours mainly on the head and neck. However, a wide range of clinical signs have been noted. The clinical presentation of FMF may include prurigo-like lesions, acneiform lesions, cysts, nodules, areas of scarring alopecia, and hypopigmented plaques or papules with follicular prominences. The average age of diagnosis is 60 years while it is rare in childhood and adolescence. We discuss the case of a 12-year-old male patient who had an asymptomatic, erythematous, infiltrating plaque across his left nasolabial fold for three months prior to presentation. Histological assessment of lesion showed characteristic findings of follicular mucinosis with predominance of CD4+ lymphocytes and immunohistochemical studies were positive for CD3+ stains. An increased CD4:CD8 ratio and negative CD20 was also shown. Both findings were consistent with diagnosis of FMF.


Mycosis Fungoides , Skin Neoplasms , Male , Adolescent , Humans , Child , Middle Aged , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Mycosis Fungoides/diagnosis , Mycosis Fungoides/chemistry , Mycosis Fungoides/pathology , Hair Follicle/chemistry , Hair Follicle/pathology
14.
Acta Derm Venereol ; 103: adv13358, 2023 Oct 03.
Article En | MEDLINE | ID: mdl-37787421

Alopecia areata is an autoimmune non-scarring disease in which the exact mechanism that induces loss of immune privilege is unknown. Zinc is important for DNA stability and repair mechanisms that are essential in maintaining normal hair growth. Zinc deficiency has been investigated as an important factor in many autoimmune diseases, and may have a possible role in the aetiopathogenesis of alopecia areata. This study included 32 patients with severe forms of alopecia areata, and 32 age- and sex-matched healthy controls. When comparing serum zinc levels in these 2 groups, statistically significantly lower zinc concentrations were found in the alopecia areata group (p = 0.017). Detected zinc deficiency was statistically more prevalent in patients with alopecia areata (p = 0.011). Evaluating patients with alopecia areata, a statistically significant negative correlation between serum zinc levels and severity of the disease was found (ρ = 0.006). The results indicate that zinc serum assessment is necessary in patients with alopecia areata. Low serum zinc levels were found to correlate with severity of alopecia areata. Given that most severe forms of alopecia areata are frequently most treatment-resistant, additional randomized control trials examining zinc supplementation are necessary to investigate its potential role in the restoration of hair follicles.


Alopecia Areata , Autoimmune Diseases , Malnutrition , Humans , Alopecia Areata/diagnosis , Hair Follicle/pathology , Malnutrition/complications , Zinc , Male , Female
15.
Am J Clin Dermatol ; 24(6): 895-912, 2023 Nov.
Article En | MEDLINE | ID: mdl-37606849

Alopecia areata is an autoimmune hair loss disease that is non-scarring and is characterized by chronic inflammation at the hair follicle level. Clinically, patients' presentation varies from patchy, circumscribed scalp involvement to total body and scalp hair loss. Current management is guided by the degree of scalp and body involvement, with topical and intralesional steroid injections as primarily first-line for mild cases and broad immunosuppressants as the mainstay for more severe cases. Until recently, the limited number of blinded, randomized, placebo-controlled clinical trials for this disease had made establishing an evidence-based treatment paradigm challenging. However, growing insights into the pathogenesis of alopecia areata through blood and tissue analysis of human lesions have identified several promising targets for therapy. T-helper (Th) 1/interferon skewing has traditionally been described as the driver of disease; however, recent investigations suggest activation of additional immune mediators, including the Th2 pathway, interleukin (IL)-9, IL-23, and IL-32, as contributors to alopecia areata pathogenesis. The landscape of alopecia areata treatment has the potential to be transformed, as several novel targeted drugs are currently undergoing clinical trials. Given the recent US FDA approval of baricitinib and ritlecitinib, Janus kinase (JAK) inhibitors are a promising drug class for treating severe alopecia areata cases. This article will review the efficacy, safety, and tolerability of current treatments for alopecia areata, and will provide an overview of the emerging therapies that are leading the revolution in the management of this challenging disease.


Alopecia Areata , Janus Kinase Inhibitors , Humans , Alopecia/pathology , Hair Follicle/pathology , Scalp/pathology , Immunosuppressive Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use
16.
Dev Cell ; 58(20): 2140-2162.e5, 2023 10 23.
Article En | MEDLINE | ID: mdl-37591247

A wealth of specialized cell populations within the skin facilitates its hair-producing, protective, sensory, and thermoregulatory functions. How the vast cell-type diversity and tissue architecture develops is largely unexplored. Here, with single-cell transcriptomics, spatial cell-type assignment, and cell-lineage tracing, we deconstruct early embryonic mouse skin during the key transitions from seemingly uniform developmental precursor states to a multilayered, multilineage epithelium, and complex dermal identity. We identify the spatiotemporal emergence of hair-follicle-inducing, muscle-supportive, and fascia-forming fibroblasts. We also demonstrate the formation of the panniculus carnosus muscle (PCM), sprouting blood vessels without pericyte coverage, and the earliest residence of mast and dendritic immune cells in skin. Finally, we identify an unexpected epithelial heterogeneity within the early single-layered epidermis and a signaling-rich periderm layer. Overall, this cellular and molecular blueprint of early skin development-which can be explored at https://kasperlab.org/tools-establishes histological landmarks and highlights unprecedented dynamic interactions among skin cells.


Epidermis , Skin , Mice , Animals , Hair Follicle/pathology , Hair , Epithelium
17.
Dev Genes Evol ; 233(2): 137-145, 2023 Dec.
Article En | MEDLINE | ID: mdl-37561178

Hair follicle growth is cyclical, and hair cycle dysfunction can lead to hair follicle-related disorders, including alopecia and hirsutism. The objective was to investigate the influence and underlying mechanism of Krüppel-like factor 4 (KLF4) overexpression on hair follicle growth and development in C57BL/6 mice. To provide a theoretical basis for the biological functions of KLF4 gene in hair follicle development and hair follicle cycle, mice were assigned to three groups: experimental, overexpressing KLF4 (Ad-KLF4); control, expressing green fluorescent protein (Ad-NC); and blank, no treatment. Fur was removed from the dorsal surface, and the mice were intradermally injected with 25 µL 1 × 1010 PFU/mL adenovirus vector (Ad-KLF4 or Ad-NC) at three points. Samples were collected for molecular biological and histological analysis. It was found that mRNA and protein levels of Wnt pathway-associated factors ß-catenin, LEF1, hair follicle cell proliferation-related factor Ki67, and hair follicle inner caledrin marker AE15 were all significantly greater in the Ad-NC and blank groups than in Ad-KLF4 mice (P < 0.01). These findings were confirmed by immunohistochemical analysis. Hair growth was monitored photographically for 14 days, showing an absence of growth in the injected region of the KLF4-overexpressing mice in contrast to non-overexpressing areas where hair growth was normal. HE staining showed that hair follicles in the blank and Ad-NC mice were normal, while those in the KLF4-overexpressing areas remained in telogen or early anagen with spherical dermal papillae situated at the edge of the dermis and subcutaneous tissue without an inner heel sheath. In conclusion, it was found that KLF4 downregulated key Wnt/ß-catenin-associated factors during follicular regeneration in mice, reducing both follicular development and growth.


Hair Follicle , beta Catenin , Animals , Mice , beta Catenin/genetics , beta Catenin/metabolism , Growth and Development , Hair Follicle/metabolism , Hair Follicle/pathology , Kruppel-Like Factor 4 , Mice, Inbred C57BL , Wnt Proteins/genetics
18.
Vet Dermatol ; 34(6): 567-575, 2023 Dec.
Article En | MEDLINE | ID: mdl-37518946

BACKGROUND: Alopecia X in Pomeranians is caused by a hair cycle deregulation, associated with downregulation of key regulatory genes of the Wnt and Shh pathways, and stem-cell markers. However, the pathogenesis remains unclear. p63 is an important transcription factor correlated with the aforementioned hair cycle modulating genes. HYPOTHESIS/OBJECTIVES: The aim of this study was to highlight possible changes of p63 immunohistochemical expression within the hair follicles in canine alopecia X compared with normal skin. ANIMALS: Skin biopsies from 19 alopecia X-affected and six control Pomeranians were analysed. MATERIALS AND METHODS: Serial histological sections of skin biopsies harbouring anagen, telogen and kenogen hair follicles were immunohistochemically evaluated for differences in p63 expression in the affected and control samples. RESULTS: Dogs with alopecia X had a significantly decreased immunoexpression of p63 in telogen and kenogen hair follicles. CONCLUSIONS AND CLINICAL RELEVANCE: The decrease of p63 immunoexpression observed in canine alopecia X suggests an involvement of p63 in hair cycle.


Dog Diseases , Hair Follicle , Dogs , Animals , Hair Follicle/pathology , Alopecia/genetics , Alopecia/veterinary , Skin/pathology , Biopsy/veterinary , Gene Expression Regulation , Dog Diseases/pathology
19.
Skin Res Technol ; 29(7): e13393, 2023 Jul.
Article En | MEDLINE | ID: mdl-37522498

BACKGROUND AND AIM: No previous study investigated the anatomical changes of the scalp and hair follicles between tertiary androgenetic alopecia and severe alopecia areata using high-resolution magnetic resonance imaging (HR-MRI). This study aimed to explore the value of HR-MRI in assessing alopecia. MATERIALS AND METHODS: Forty-eight people were included in this study. The imaging indicators of the vertex and occipital scalp were recorded and compared. The logistic regression model was developed for the indicators that differed between tertiary androgenetic alopecia and severe alopecia areata. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic efficacy of the model for tertiary androgenetic alopecia and severe alopecia areata. RESULTS: At the vertex, the thickness of the subcutaneous tissue layer, follicle depth, relative follicle depth, total number of follicles within a 2-cm distance, and number of strands reaching the middle and upper third of the subcutaneous fat layer within a 2-cm distance were statistically different between patients with tertiary androgenetic alopecia, those with severe alopecia areata, and healthy volunteers (p < 0.05). The logistic regression model suggested that the subcutaneous tissue layer thickness was important in discriminating tertiary androgenetic alopecia from severe alopecia areata. The ROC curve showed that the area under the curve, sensitivity, specificity, and best cutoff values of the subcutaneous tissue layer were 0.886, 94.4%, 70%, and 4.31 mm, respectively. CONCLUSIONS: HR-MRI can observe the changes in anatomical structures of the scalp and hair follicles in patients with alopecia. HR-MRI can be applied to the differential diagnosis of tertiary androgenetic alopecia and severe alopecia areata.


Alopecia Areata , Humans , Alopecia Areata/diagnostic imaging , Alopecia Areata/pathology , Diagnosis, Differential , Alopecia/diagnostic imaging , Alopecia/pathology , Hair Follicle/diagnostic imaging , Hair Follicle/pathology , Scalp/diagnostic imaging , Scalp/pathology , Magnetic Resonance Imaging
20.
Vet Pathol ; 60(6): 910-914, 2023 11.
Article En | MEDLINE | ID: mdl-37408382

There have been unpublished reports of a follicular dysplastic syndrome in adult white-tailed deer (Odocoileus virginianus; WTD), known colloquially as "toothpaste hair disease." The current report aims to describe the gross and histologic lesions in skin samples from 2 adult WTDs that presented to the Wisconsin Department of Natural Resources and the Wisconsin Veterinary Diagnostic Laboratory with reports of hair loss in 2018. Both cases were grossly alopecic with sparing of the distal extremities and variably the head and neck. Histologic features included hair follicles and adnexa present in relatively normal numbers, dilated and misshapen follicles, and dysplastic hair bulbs. Hair follicles were empty, contained fragmented and irregular hair shafts, or contained concretions of keratin. Hair bulbs were rarely infiltrated by small lymphocytes, suggestive of alopecia areata as a cause of the gross appearance. This condition does not appear to be directly responsible for WTD mortality but presumably would predispose affected animals to greater environmental exposure. Evaluation of additional affected individuals is warranted to further evaluate for features of alopecia areata.


Alopecia Areata , Deer , Animals , Alopecia Areata/pathology , Alopecia Areata/veterinary , Hair Follicle/pathology
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