Hair Follicle Differentiation Research Articles

Role of HFSCARC in hair follicle stem cell proliferation and differentiation in cashmere goat

AbstractAs a model of regenerative medicine, hair follicle stem cell (HFSC) plays a determining role in the hair cycle. Emerging evidences showed that long noncoding RNAs regulated the biological function of HFSC. In this current study, we found that lncRNA‐000552, standing for “goat secondary HFSC Associated SYNE3 Regulator of HF Cycle” (HFSCARC) expressed higher in anagen than that in telogen of cashmere goat. Through experiments involving nucleocytoplasmic separation and RNA‐FISH, we determined that HFSCARC was primarily located in the nucleus of HFSC. To understand the function of HFSCARC, the study performed various assays, including crystal violet staining, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, EdU, and flow cytometry analysis, which collectively revealed that HFSCARC inhibited HFSC proliferation. Additionally, HFSCARC promoted the differentiation of HFSC by investigating the expression of marker genes specific to stem cells and keratinocytes. RNA sequencing analysis was conducted to investigate the global gene expression changes associated with HFSCARC expression. The results showed that HFSCARC altered the expression of genes involved in cell proliferation, hair follicle development, and regulation of bone morphogenetic proteins (BMP) signaling. Furthermore, the study revealed that HFSCARC activated the BMP signaling pathway. Intriguingly, the study found a decreased expression of SYNE3, which was a neighboring gene of HFSCARC. The altered expression of genes associated with transmethylase and demethylase further suggested that HFSCARC might play an important role in regulating the SYNE3 expression. Overall, this study provides valuable insights into the regulatory role of HFSCARC in the biological function of HFSC. These findings contribute to a better understanding of the involvement of noncoding RNAs in the regulation of hair cycle.

Denticleless E3 ubiquitin protein ligase (DTL) maintains the proliferation and differentiation of epidermis and hair follicles during skin development.

A precise balance between the proliferation and differentiation of epidermal progenitors is required to achieve the barrier function during the development of epidermis. During the entire process of skin development, the newly formed basal layer cells divide, differentiate, and migrate outward to the surface of the skin, which is tightly regulated by a series of events related to cell cycle progression. The CRL4DTL complex (Cullin 4 RING ligase, in association with the substrate receptor DTL) has long emerged as a master regulator in various cellular processes, which mediates the degradation of key cell cycle proteins. However, the roles of DTL in regulating epidermal morphogenesis during skin development remain unclear. We showed that DTL deficiency in epidermal progenitor cells leads to defects in epidermal stratification and loss of hair follicles accompanied by reduced epidermal progenitor cells and disturbed cell cycle progression during skin development. Transcriptome analysis revealed that p53 pathway is activated in DTL-depleted epidermal progenitor cells. The apoptosis of epidermal cells showed in DTL deficiency mice is rescued by the absence of p53, but the proliferation and differentiation defects were p53-independent. Our findings indicate that DTL plays a vital role in epidermal malformation during skin development.

Astragalus membranaceus and Cinnamomum cassia Stimulate the Hair Follicle Differentiation-Related Growth Factor by the Wnt/β-Catenin Signaling Pathway.

Astragalus membranaceus and Cinnamomum cassia are used as spices and flavorful ingredients, or medicinal herbs with pharmacological effects. In this study, the hair-growth-promoting effects of the YH complex, a newly developed formula consisting of membranaceus and C. cassia, are investigated with the prediction of its molecular mechanism. The target gene of the YH complex was about 74.8% overlapped with the gene set of 'Hair growth' on the GO Biological Process database. The oral administration of the YH complex promoted hair regrowth and increased hair-shaft thickness in depilated hair loss mice. In addition, the anagen/telogen hair follicle ratio was significantly increased by the YH complex. The growth factors affecting the growth of hair follicles were dose-dependently increased by treatment with the YH complex. The Wnt/β-catenin signaling pathway expressions in skin tissues were apparently increased by the administration of the YH complex. In conclusion, the YH complex consisting of A. membranaceus and C. cassia induced hair follicle differentiation and preserved the growing-anagen phase by increasing growth factors and the Wnt/β-catenin signaling pathway, leading to the restoration of hair loss. The YH complex can be a remedy for hair loss diseases, such as alopecia areata, androgenetic alopecia, telogen effluvium, and chemotherapy-induced alopecia.

The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles.

An increasing number of studies show that vascular endothelial growth factor is an important regulator of hair growth, and involves in processes of hair follicle development by vascularization. Recently, VEGF receptor-2 (VEGFR-2) has been detected in epithelial cells of hair follicles, indicating that it may have a direct role in the biological activity of hair follicles. To explore how VEGFR-2 regulates hair follicle development, we investigated the co-expression pattern of VEGFR-2 with β-catenin, Bax, Bcl-2, involucrin, AE13 (hair cortex cytokeratin), keratin 16, keratin 14, and Laminin 5 by immunofluorescence double staining in anagen hair follicles of normal human scalp skin. The results of double staining immunofluorescence showed a strong overlapping and similar expression pattern for VEGFR-2 with β-catenin and Bcl-2, and revealing associated expression pattern with involucrin, AE13, keratin 14, keratin 16, and Laminin 5. These results elucidated that VEGFR-2 activation may participate in hair follicle differentiation, proliferation, and apoptosis in vivo.

TRPS1: A Marker of Follicular Differentiation.

The trichorhinophalangeal syndrome type 1 (TRPS1) immunohistochemical (IHC) stain has increased in use in recent years as a marker for breast carcinomas. The TRPS1 gene is involved in various tissues, including the growth and differentiation of hair follicles. This article seeks to evaluate the IHC expression of TRPS1 in cutaneous neoplasms with follicular differentiation, such as trichoblastoma (TB), trichoepithelioma (TE), and basal cell carcinoma (BCC). IHC studies were performed on 13 TBs, 15 TEs, and 15 BCCs with an antibody against TRPS1. The study found a variable staining expression of TRPS1 in the tumor nests of TB, TE, and BCC. BCCs were distinct in that none of the BCCs demonstrated intermediate or high positivity, while TBs and TEs showed intermediate-to-high positivity in 5/13 (38%) and 3/15 (20%) of cases, respectively. We observed a distinct staining pattern among the mesenchymal cells of TB and TE. We found that TRPS1 highlighted perifollicular mesenchymal cells adjacent to the nests of TB and TE tumor cells. This staining pattern was absent in BCCs, where only scattered stromal cells were positive for TRPS1. Papillary mesenchymal bodies were also highlighted by TRPS1 in TB and TE. TRPS1 stained various parts of the normal hair follicle, including the nuclei of cells in the germinal matrix, outer root sheaths, and hair papillae. TRPS1 may be a useful IHC marker for follicular differentiation.

Hair follicle stem cell proliferation and differentiation are achieved by miR-1285-3P through targeted regulation of NOTCH pathway

The purpose of this experiment is to understand how miR-1285-3P regulates the NOTCH signaling pathway by targeting, thereby affecting the proliferation and differentiation of hair follicle stem cells. The cultured Inner Mongolia hair follicle stem cells were used in this experiment, and they were divided into control group, blank transfection group and miR-1285-3P transfection group. Among them, the control group was left untreated; the blank group was given miR-NC transfection; at the same time, the miR-1285-3P transfection group was given miR-1285-3P mimics for transfection. Compared with the control group (97.24 ± 6.81) and blank gro transfection up (97.32 ± 7.20), the cell proliferation ability of the miR-1285-3P transfection group (49.31 ± 3.39) was significantly lower. Compared with the other two groups, The proliferation ability of cells in the miR-1285-3P transfection group was decreased (P < 0.05); compared with the S-phase hair follicle stem cells in the control group (19.23 ± 1.29) and blank transfection group (19.38 ± 1.45), the miR-1285-3P transfection group (15.26 ± 1.26) decreased more significantly (P < 0.05). For hair follicle stem cells in each group, the proportion of cells in the G0-G1 phase was significantly different between the blank transfection group (63.18 ± 2.78) and the control group (64.29 ± 2.09), and the blank transfection group had a higher proportion (P < 0.05). In the process of miR-1285-3P targeting and regulating NOTCH signaling pathway, the proliferation and differentiation ability of hair follicle stem cells is affected. When NOTCH signaling pathway is activated, the differentiation of hair follicle stem cells is accelerated.

Melatonin promotes the development of the secondary hair follicles by regulating circMPP5

BackgroundThe quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats. The higher the density of secondary hair follicles, the higher the quality and yield of cashmere from the fleece. Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth. Preliminary experimental results from our laboratory showed that melatonin (MT) treatment of goat kids after their birth could increase the density of secondary hair follicles and, thus, improve the subsequent yield and quality of cashmere. These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein, and from a reduction in apoptosis. The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.ResultsMT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere, and this dominant effect continued to the second year. Melatonin promotes the proliferation of secondary hair follicle cells at an early age. The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year. The genome-wide data results involved KEGG analysis of 1044 DEmRNAs, 91 DElncRNAs, 1054 DEcircRNAs, and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the development of secondary hair follicles, with key genes (FGF2, FGF21, FGFR3, MAPK3 (ERK1)) being up-regulated and expressed. We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3.ConclusionsWe conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211, regulating the expression of MAPK3, to induce the differentiation and proliferation of secondary hair follicle cells.In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells. Collectively, these events increase the numbers of secondary hair follicles, thus improving the production of cashmere from these goats.

SERUM VITAMIN D3 LEVELS IN PATIENTS WITH TELOGEN EFFLUVIUM IN DUHOK GOVERNORATE

Background: Telogen effluvium, a commonly reported problem, strictly affect the quality of life of the patients. Vitamin D stimulates differentiation of hair follicles. The association between serum vitamin D levels and telogen effluvium describe in several studies. The aim of study was to determine serum level of vitamin D in patients with telogen effluvium and analyze the relationship of altered serum total vitamin D levels with Telogen effluvium.

Co-Expression Pattern of Artemis Serine 516 Phosphorylation with Indicators Involving in Differentiation, Proliferation and Apoptosis of Human Anagen Hair Follicles: An Immunofluorescence Double-Staining Study.

Artemis belongs to the SNM1 gene family, and plays a role in repairing ionizing-radiation-induced DNA double-strand breaks and variable (diversity) joining recombination. S534, S538, S516, S645 represent four most rapid phosphorylation sites in Artemis, and serine phosphorylation at amino acid 516 is closely associated with activation. Artemis mutation is perceived as contributing to Omenn syndrome, which manifest features of severe combined immunodeficiency disease, associated with lymphadenopathy, hepatosplenomegaly, erythroderma and baldness. In addition, Artemis phosphorylated at serine 516 (Artemis S516-P) was expressed in scalp hair follicles (HF) as well as other skin appendages, and its expression level is important to mouse hair cycling. However, whether Artemis participated in the regulation of HF growth still unclear. Using immunofluorescence double-staining, we assessed the association between Artemis S516-P with proliferation, apoptosis, and differentiation markers in normal adult anagen scalp HF. The results of double-staining immunofluorescence revealed overlapping expression pattern for Artemis S516-P and keratin16, similar pattern for c-myc and p21, while presenting opposite trends for keratin 10, phospho-p53, Bax, Bcl-2 and keratin 14. Our study provides the clues that Artemis may play roles in regulation of differentiation, proliferation, apoptosis and cell cycling during HF growth and development.

Trichoblastomas derived from the facial skin with tactile hair in aged house musk shrews (Suncus murinus)

BackgroundBenign hair follicle tumors are relatively rare cutaneous neoplasms arising from hair follicle differentiation. These tumors are slow-growing solitary papules or nodules in the head, face or neck. The aim of this study was to describe 2 cases of trichoblastomas in tactile hair skin incidentally encountered in aged house musk shrews (Suncus murinus). In addition, this case report clarifies whether the characteristics in the tactile hair skin of Suncus murinus are different from those in humans and other animals.Case presentationThe animals were investigated the characteristics of the clinical findings, hematological and serum biochemical profiles (particularly, serum amyloid A levels (vSAA)), and histopathological results. Suncus murinus with the facial tumor showed weight loss and coarse fur. Hematological examinations indicated microcytic and normochromic anemia. Although few apparent changes were serum biochemically found in Suncus murinus, vSAA levels moderately increased and revealed inflammatory reactions. These lesions histopathologically showed the basaloid islands comprising peripheral palisading and dilated microcysts containing variable admixtures of free-floating cells such as neoplasm cells, giant cells, clear cells, mononuclear cells and erythrocytes.ConclusionsThe author concluded that trichoblastomas in Suncus murinus revealed growth and morphological characteristics that recapitulate part of embryological development in the tactile hair follicles. In the histological structure, their trichoblastomas in the tactile hair skin were different from those found in humans and animals such as cats, dogs and other wildlife.

The origins of skin diversity: lessons from dermal fibroblasts.

Skin is largely composed of an epidermis that overlies a supporting dermis. Recent advancements in our understanding of how diverse groups of dermal fibroblasts regulate epidermal and hair follicle growth and differentiation have been fueled by tools capable of resolving molecular heterogeneity at a single-cell level. Fibroblast heterogeneity can be traced back to their developmental origin before their segregation into spatially distinct fibroblast subtypes. The mechanisms that drive this lineage diversification during development are being unraveled, with studies showing that both large- and small-scale positional signals play important roles during dermal development. Here, we first delineate what is known about the origins of the dermis and the central role of Wnt/β-catenin signaling in its specification across anatomical locations. We then discuss how one of the first morphologically recognizable fibroblast subtypes, the hair follicle dermal condensate lineage, emerges. Leveraging the natural variation of skin and its appendages between species and between different anatomical locations, these collective studies have identified shared and divergent factors that contribute to the extraordinary diversity of skin.

HISTOPATHOLOGICAL SPECTRUM OF SKIN APPENDAGEAL TUMORS AND TUMOR LIKE LESIONS

Introduction: The skin appendageal tumors are large group of neoplasm that originates from multipotential stem cells. They exhibit morphologic differentiation towards one of the four primary adnexal structures. To study the histopat Aim: hological spectrum of skin appendageal tumors and tumor like lesions. Our study is partly retrospective and prospective. All hist Materials And Methods: opathologically diagnosed skin appendageal lesions were reviewed and results were tabulated. 56 cases of Results: skin appendageal lesions were diagnosed during the study period. Predominant lesions were neoplastic (89.28%) while remaining were tumor like lesions(10.72%). The large variety of tumors were benign (66.07%) in nature. The most common line of differentiation was towards sweat gland, followed by hair follicle and sebaceous differentiation with 25(44.64%), 18(32.14%) and 13(23.22%) cases respectively. The skin appendageal tumors are the rare a Conclusion: nd most clinically misdiagnosed neoplasms, thus diagnosis relies on histological evaluation.

601 Pharmacological inhibition of the chemokine receptor CX3CR1 promotes hair growth

Macrophages are located around hair follicles in normal skin and typically peak in density during the mid-telogen stage of the hair cycle. Hair follicles chemotactically attract macrophages and T cells and are in range to regulate hair follicle stem cells (HFSCs) quiescence, proliferation, and differentiation during physiologic and injured states. The expression of the fractalkine receptor CX3CR1 has been identified as a key regulator of macrophage and T cell migration and function at sites of inflammation.

LB1019 The early region of trichodysplasia spinulosa polyomavirus drives proliferation, altered differentiation, and ectopic expression of hair follicle differentiation markers in interfollicular tail epidermis

Trichodysplasia spinulosa (TS) is a rare hair follicle disorder that develops in immunosuppressed patients and is associated with productive infection by the TSPyV polyomavirus. Affected follicles contain an attenuated hair matrix, expanded compartment of aberrantly proliferating inner root sheath (IRS)-like cells containing viral particles, and a disorganized mass of hair shaft-like cells. The expression of viral early region (ER) genes encoding T antigens (TAgs) that drive cellular proliferation and viral genome replication is tightly restricted to hair follicle matrix cells and IRS-like cells.

Effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep.

The effects of androgens on human skin mainly include the regulation of growth and differentiation of hair follicles and sebaceous glands. Androgens may have some physiological roles in sheep skin that are similar to those of humans, but further confirmation is needed. Therefore, Hetian sheep were chosen in this study as an animal model to explore the effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep. The sheep were treated with different concentrations of testosterone for 42days. Skin tissue sections were prepared and then subjected to hematoxylin-eosin, Sacpic, Masson's trichrome, and Oil Red O staining to observe changes in skin morphology. Changes in the content of blood-related factors were also detected using ELISA kits. The skin tissue distribution of androgen receptor was explored by immunohistochemistry and immunofluorescence assays. The results showed that testosterone significantly increases the sebaceous gland area and stimulates the formation of new sebaceous glands. Further exploration revealed that testosterone promotes the proliferation of sebaceous gland juvenile cells. However, testosterone was found to have no significant effect on hair follicle density and hair follicle structure. Testosterone increased dihydrotestosterone levels but decreased 5α-reductase 1 and 5α-reductase 2 levels. The androgen receptors were distributed in the hair follicles, sebaceous glands, and some major skin appendages of Hetian sheep. This study suggests that androgens can be effective in regulating sebum production in sheep. This study will help advance research efforts to further explore the molecular and cellular mechanisms by which androgens modify sheep follicles and sebaceous glands.

Clinicopathological Study of Skin Adnexal Tumors with Special Emphasis on the Line of Differentiation

Background: Skin is a complex organ composed of epidermis, dermis and skin adnexa producing multitude of tumors. The skin adnexal neoplasms are classified into sub-groups, depending on their differentiation towards hair follicles, sebaceous, apocrine and eccrine glands. Clinically adnexal neoplasm presents as asymptomatic papules or nodules, having non-specific morphological appearance and therefore histopathology is the gold standard for their confirmatory diagnosis. The aim is to assess clinico-histopathological characteristic features of the skin lesions, subtype and to pick up certain subtle features that clinch the diagnosis towards their line of differentiation. Methods: The study has been conducted in the Department of Pathology, for a period of one year. The total numbers of cases with histopathological diagnosis of skin adnexal lesions are 105. Ethical clearance for the same has been obtained by the Head of Institution. Skin biopsy specimen are received and processed in the histokinette; paraffin embedded blocks made and stained with Hematoxylin &amp; Eosin stain. Special stains when required have been used. Descriptive statistics have been used in analysis of the results. Result: The total number of cases with histopathological diagnosis of skin adnexal lesions is 105. Among them 99/105 cases (94.3%) are benign and malignant counterparts comprised of 6/105 cases (5.7%).Overall lesions with hair follicle differentiation comprised of 73.3% (77/105), followed by sebaceous differentiation of 15.3% (16/105) and eccrine differentiation of 11.4 % (12/105). Conclusion: This study emphasized that histopathological examination, plays an essential role in studying the skin adnexal tumors, owing to its indistinctive clinical presentation. Keywords: Adnexal, Eccrine, Skin, Tumor, Sebaceous, Apocrine

Characterization of Plant-Based Biotin from SesZenBioTM and In silico Studies to Prove Its Potential in Hair Care

A standardized extract from Sesbania agati leaves (SESAL) was developed by Zenherb labs Pvt. Ltd., Mumbai, and is one of its kind plant-based biotin supplements. The current work aimed at characterization of SESAL using chromatographic techniques (like HPLC &amp; HPTLC) and DNA authentication. Additionally, an in-silico approach (docking) was also adopted to predict the molecular interactions and probable mechanisms involved in potential role of SESAL in hair care products range. Drug likeliness was assessed on the basis of ADMET properties and Lipinski’s Rule of 5. DNA fingerprinting followed by HPTLC confirmed the identification and authentication. The biotin content in SesZenBio was estimated to be 0.5% by validated HPLC method. Mechanistically, biotin along with 2 other cofactors in SesZenBioTM is predicted to stimulate the hair follicle growth and differentiation, thus improving hair health. SesZenBioTM might hold 2x potential as against synthetic biotin in hair care applications.

Evaluating the Role of lncRNAs in the Incidence of Cardiovascular Diseases in Androgenetic Alopecia Patients.

Hair loss occurs in patients with Androgenetic Alopecia (AGA). The pattern of hair loss is different between men and women. The main cause of hair loss is increased cell apoptosis and decreased regeneration, proliferation and differentiation processes in hair follicles. Long Non-Coding RNAs (lncRNAs) are one of the most important molecules that regulate the processes of apoptosis, regeneration, proliferation and differentiation in hair follicles. Since studies have shown that lncRNAs can be effective in the development of cardiotoxicity and induction of cardiovascular disease (CVD); so effective lncRNAs in the regulation of regeneration, proliferation, differentiation and apoptosis of hair follicles can be involved in the development of CVD in AGA patients with. Therefore, this study investigated the lncRNAs involved in increasing apoptosis and reducing the processes of regeneration, proliferation and differentiation of hair follicles. The aim of the current study was to evaluate the role of lncRNAs as a risk factor in the incidence of CVD in AGA patients; it will help to design treatment strategies by targeting signaling pathways without any cardiotoxicity complications.

A Hairy Cituation – PADIs in Regeneration and Alopecia

In this Review article, we focus on delineating the expression and function of Peptidyl Arginine Delminases (PADIs) in the hair follicle stem cell lineage and in inflammatory alopecia. We outline our current understanding of cellular processes influenced by protein citrullination, the PADI mediated posttranslational enzymatic conversion of arginine to citrulline, by exploring citrullinomes from normal and inflamed tissues. Drawing from other stem cell lineages, we detail the potential function of PADIs and specific citrullinated protein residues in hair follicle stem cell activation, lineage specification and differentiation. We highlight PADI3 as a mediator of hair shaft differentiation and display why mutations in PADI3 are linked to human alopecia. Furthermore, we propose mechanisms of PADI4 dependent fine-tuning of the hair follicle lineage progression. Finally, we discuss citrullination in the context of inflammatory alopecia. We present how infiltrating neutrophils establish a citrullination-driven self-perpetuating proinflammatory circuitry resulting in T-cell recruitment and activation contributing to hair follicle degeneration. In summary, we aim to provide a comprehensive perspective on how citrullination modulates hair follicle regeneration and contributes to inflammatory alopecia.

Role of vitamin D in hair loss: A short review.

Vitamin D, a vitamin and hormone, plays an important role in dermatology and dermatotherapeutics, due to its anti-inflammatory and immunomodulatory properties, and regulation of keratinocyte differentiation and proliferation. It also affects the hair cycle, and its role in hair loss is under constant research. This review aims to give a brief overview of vitamin D biology within the hair follicle, role in the etiopathogenesis, and rationale for supplementation in various alopecias. A PubMed literature search was performed to review relevant current literature and studies investigating the role of vitamin D in the etiopathogenesis, as a supplement and a potential therapeutic modality in hair loss. Vitamin D is intricately involved in various signaling pathways of growth and differentiation of hair follicles. Most studies show an inverse relationship between serum vitamin D levels and non-scarring alopecias such as telogen effluvium, androgenetic alopecia, alopecia areata, and trichotillomania. Vitamin D deficiency is also associated with scarring alopecia. However, conclusive studies to demonstrate the benefit of vitamin D administration in correcting hair loss and managing these conditions are lacking. Hence, further studies are needed before vitamin D can be routinely recommended as a treatment modality in these conditions.