Combining multiomics to analyze the molecular mechanism of hair follicle cycle change in cashmere goats from Inner Mongolia.

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep.Inner Mongolia Cashmere Goat is a local excellent breed of cashmere and meat dual-purpose, which is a typical heterogeneous indumentum. The hair follicles cycle through periods of vigorous growth (anagen), a regression caused by apoptosis (catagen), and relative rest (telogen). At present, it is not clear which genes affect the cycle transformation of hair follicles and unclear how proteins impact the creation and expansion of hair follicles.we using multi-omics joint analysis methodologies to investigated the possible pathways of transformation and apoptosis in goat hair follicles. The results showed that 917,1,187, and 716 proteins were specifically expressed in anagen, catagen andtelogen. The result of gene ontology (GO) annotation showed that differentially expressed proteins (DEPs) are in different growth cycle periods, and enriched GO items are mostly related to the transformation of cells and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment result indicated that the apoptosis process has a great impact on hair follicle's growth cycle. The results of the protein interaction network of differential proteins showed that the ribosomal protein family (RPL4, RPL8, RPS16, RPS18, RPS2, RPS27A, RPS3) was the core protein in the network. The results of combined transcriptome and proteomics analysis showed that there were 16,34, and 26 overlapped DEGs and DEPs in the comparison of anagen VS catagen, catagen VS telogen and anagen VS telogen, of which API5 plays an important role in regulating protein and gene expression levels. We focused on API5 and Ribosomal protein and found that API5 affected the apoptosis process of hair follicles, and ribosomal protein was highly expressed in the resting stage of hair follicles. They are both useful as molecular marker candidate genes to study hair follicle growth and apoptosis,and they both have an essential function in the cycle transition process of hair follicles. The results of this study may provide a theoretical basis for further research on the growth and development of hair follicles in Inner Mongolian Cashmere goats.

Pilar Cyst of the Dorsal Hand: A Rare Presentation of a Common Cyst.

Pilar cysts are common benign cysts of follicular origin that typically arise in areas of skin containing dense hair follicles such as the scalp. Here we describe a unique case of a young woman who was found to have a pilar cyst on the dorsum of her hand, a rather atypical location given the relative lack of pilosebaceous units. This case illustrates the variability in pilar cyst presentation and the importance of considering a pilar cyst in the differential diagnosis of a patient presenting with a tumor of the dorsal hand.

Effects of Cudrania tricuspidata and Sargassum fusiforme extracts on hair growth in C57BL/6 mice.

BACKGROUND: Cudrania tricuspidata is a perennial plant, and Sargassum fusiforme is a brown seaweed with numerous potential benefits, including anticancer, anti-inflammatory, and antioxidant activities. However, the efficacies of C. tricuspidata and S. fusiforme on hair growth have not yet been elucidated. Therefore, the present study examined the effects of C. tricuspidata and S. fusiforme extracts on hair growth in C57BL/6 mice. RESULTS: ImageJ demonstrated that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts significantly increased the hair growth rate in the dorsal skin of C57BL/6 mice compared to the control group. Histological analysis confirmed that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts for 21 days significantly increased the length of hair follicles on the dorsal skin of treated C57BL/6 mice compared to that in the control mice. RNA sequencing analysis revealed that hair growth cycle-related factors (anagen factors) such as Catenin Beta 1 (Ctnnb1) and platelet-derived growth factor (Pdgf) were upregulated (> twofold) only by C. tricuspidate extracts, whereas vascular endothelial growth factor (Vegf) and Wnts were upregulated by both C. tricuspidata or S. fusiforme applications in treated mice (compared to the control mice). In addition, oncostatin M (Osm, a catagen-telogen factor) was downregulated (< 0.5 fold) by C. tricuspidata when administered via both skin and drinking mode in treated mice compared to that in control mice. CONCLUSIONS: Our results suggest that C. tricuspidata and/or S. fusiforme extracts show potential hair growth efficacy by upregulating anagen factor genes, including ß-catenin, Pdgf, Vegf, and Wnts, and downregulating catagen-telogen factor genes, including Osm, in C57BL/6 mice. The findings suggest that C. tricuspidata and/or S. fusiforme extracts are potential drug candidates to treat alopecia.

Construction of transcriptome atlas of white yak hair follicle during anagen and catagen using single-cell RNA sequencing.

BACKGROUND: As the direct organ of villus, hair follicles have obvious seasonal cycles. The hair follicle cycle is orchestrated by multiple cell types that together direct cell renewal and differentiation. But the regulation property of hair follicle cells from anagen to catagen in yak is still unknown. RESULTS: In this study, single-cell RNA sequencing was performed on 24,124 single cells of the scapular skin from white yak. Based on tSNE cluster analysis, the cell types of IFE-DC, epidermal cell lines, fibroblasts, keratinocytes, IRS, DS, INFU, and other cells in yak hair follicles during anagen and catagen were successfully identified, and the gene expression profiles were described. The GO enrichment analysis indicated the different cells characteristic genes to be mainly enriched in the epidermal development, epithelial cell differentiation and wound healing pathways. The pseudotime trajectory analysis described the differentiation trajectory of the epidermal lineage and dermal lineage of the hair follicle during anagen and catagen. Moreover, the dynamic changes of the genes like LHX2, KRT25, and KRT71 were found to be highly expressed in HS and IRS, but not in the IFE-DC, INFU, and keratinocyte during differentiation. CONCLUSIONS: Our results analyzed the time-varying process of gene expression in the dermal cell lineage and epidermal cell lineage of hair follicles during anagen and catagen during fate differentiation was expounded at the single cell level, revealing the law of fate specialization of different types of cells. In addition, based on the enrichment analysis, the transcriptional regulatory factors involved in the different cell fates were also revealed. These results will help to enhance our understanding of yak hair follicle cycle and promote the development and utilization of yak villus.

Expression of Protein Kinases RIPK-1 and RIPK-3 in Mouse and Human Hair Follicle.

Expression of cell death regulators RIPK-1 and RIPK-3 in mouse and human hair follicle structures was studied by immunohistochemistry. At anagen and catagen stages of mouse hair follicle, RIPK-1+ cells were located in the inner root sheath, whereas RIPK-3+ cells were found in the inner and outer root sheath, dermal papilla, and interfollicular epidermis. RIPK-1 expression intensity was low in the early anagen and increased as mature anagen and catagen approached. RIPK-1+ and RIPK-3+ cells were also found in human hair follicle. It is assumed that the role of necroptosis markers in hair follicle life activity is independent of programmed cell death and that they may have yet unknown functions and take part in noncanonical signal cascades.

A quantitative method for selecting a hair for nulear DNA analysis.

This study evaluated a quantitative method to predict the success of nuclear DNA (nuDNA) typing for head hair roots, using the minor-groove DNA binding dye, 4', 6-diamidino-2-phenylindole (DAPI). The procedure was successful in staining nuclear material in hair roots, regardless of soft tissue presence or growth phase. We found that the dye can even reveal an abundance of visible nuclei in hairs that were previously assumed to be unsuitable for nuDNA analysis (e.g., telogen hairs). The value of DAPI staining is particularly evident when considering the STR typing results for telogen hairs. Here, telogen hairs with greater than 100 visible nuclei frequently produced full or high-partial STR profiles, while telogen hairs with fewer than 100 visible nuclei rarely resulted in >20 % STR allele recovery. In addition, our findings indicated no interference by DAPI in the forensic examination of hair evidence, including preparation of hairs on microscopic slides, microscopic examination, DNA extraction, quantitative PCR, and short tandem repeat (STR) typing. Furthermore, the method remained steadfast for hairs washed by sonication as well as hairs retrieved from Permount™ mounting medium. When validated, this simple, quick, and quantitative screening method can be used in casework to select a hair for nuDNA analysis, especially for hairs that were previously sent directly for mitochondrial (mt) DNA analysis based on the lack of adhering soft tissue, regardless of growth phase. Conversely, nuDNA degradation may exist in hairs which exhibit microscopic characteristics typically associated with a potential to generate successful nuclear DNA profile including stretched roots with attached root sheath. DAPI staining of hairs gives forensic examiners the ability to have more information, other than growth phase, when selecting a hair or hairs for possible nuDNA analysis.

Immune cell regulation of the hair cycle.

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

Sequential cyclic changes of hair roots revealed by dermoscopy demonstrate a progressive mechanism of diffuse alopecia areata over time.

BACKGROUND: Diffuse alopecia areata (DAA) often leads to a complete hair shedding within a few months. OBJECTIVE: To explore features and mechanisms underlying DAA. MATERIALS AND METHODS: Scalp and hair root dermoscopy were conducted on 23 DAA patients throughout the disease process, 20 patchy Alopecia areata patients, 23 acute telogen effluvium (ATE) patients and 10 normal controls. Histopathology was also evaluated. RESULTS: We found almost all hair roots were anagen in early stage DAA in 18 patients (18/23, 78.3%) within the first 4-8 weeks after hair loss onset. Anagen effluvium (~4 weeks) was followed by catagen (~4 weeks) and then telogen/exogen (~8 weeks) effluvium with overlap. Hair root and proximal hair shaft depigmentation was more prominent in later DAA disease stages. Black dots, exclamation mark hairs and inconsistent thickness of hair shafts were found more often in early than later DAA (Ps < 0.01). Early DAA histopathology revealed more prominent inflammation and hair follicle regression than that observed in the later stages. Patchy alopecia areata patients showed mixed anagen, catagen and telogen hair roots while ATE patients showed increased exogen and mildly decreased hair root pigmentation. CONCLUSION: Sequential cyclic staging of shed hairs in DAA indicates the insult may be hair-cycle specific. We suggest that DAA is initially an anagen effluvium disease involving an intense inflammatory insult, later progressing to a brief catagen effluvium, and then to telogen effluvium with premature exogen, in later stages of DAA.

[The aspects of the molecular-genetic investigations of human hair depending on its morphological characteristics. I. Prognostic screening]. / Aspekty molekuliarno-geneticheskogo issledovaniia volos cheloveka v zavisimosti ot ikh morfologicheskikh kharakteristik. I. Prognosticheskii skrining.

The objective of the present work was to develop the method for the selection of hairs suitable for the molecular-genetic investigation of nuclear DNA. It was proposed to distinguish between five groups of hair depending on its growth phase, the presence or absence of epithelial tissues at the root terminus. An algorithm was developed for carrying out prognostic screening including the morphological and cytomorphological investigations the results of which can be used to evaluate the possibility for further genotyping.

Hair disorders in patients with cancer.

Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders, including alopecia, hirsutism, hypertrichosis, and pigmentary and textural hair changes. The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy-induced alopecia has been well documented primarily in the oncology literature; however, the effect of other alterations, such as radiation-induced alopecia, hirsutism, and changes in hair color or texture on quality of life have not been described. This article reviews clinically significant therapy-related hair disorders in oncology patients, including the underlying pathophysiological mechanisms, severity grading scales, patient-reported quality of life questionnaires, management strategies, and future translational research opportunities.

The Follicle Cycle in Brief.

This chapter presents a very succinct overview of the cyclic biology of the hair follicle as it transitions from the quiescent telogen stage to the anagen stage in which hairs are actively produced before regressing through the catagen stage to telogen.

Anti-CXCL4 monoclonal antibody accelerates telogen to anagen transition and attenuates apoptosis of the hair follicle in mice.

Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb). Histomorphometric analysis indicated that anti-CXCL4 mAb induced an earlier anagen phase and delayed hair follicle regression, in contrast with that in the control group. Moreover, CXCL4 mAb upregulated the transcription levels of several hair growth-related genes, including Lef1, Wnt10b, Bmp4 and Bmp2. In addition, CXCL4 mAb increased the levels of the proliferation-related protein PCNA and Bcl-2 during the anagen phase, while it reduced the expression of pro-apoptotic protein Bax and cleaved caspase-3 during the catagen phase. These findings reveal that CXCL4 plays an important role in hair growth, and that blockade of CXCL4 activity promotes hair growth.

Effect of miR-125b on dermal papilla cells of goat secondary hair follicle

Background: MicroRNAs (miRNAs) are endogenous noncoding RNAs that regulate various biological processes. miR-125b is a miRNA that has been reported to be critical for hair follicle (HF) morphogenesis and development. We identified that the expression of miR-125b varies during an individual hair cycle (anagen, catagen, and telogen) in the skin of cashmere goats. We constructed a gain model (by overexpressing miR-125b) and a loss model (by inhibiting endogenous miR-125b) based on dermal papilla cells (DPCs) to further investigate the role of miR-125b in HF cycle. In addition, we used a dual-luciferase system to highlight the predicated target genes of miR-125b. Results: We found that miR-125b affects the expression of FGF5, IGF-1, SHH, TNF-α, MSX2, LEF-1, FGF7, NOGGIN, BMP2, BMP4, TGF-ß1, and ß-catenin. The dual-luciferase assay further validated a direct interaction between miR-125b and FGF5 and TNF-α. Conclusion: miR-125b affects the expression levels of genes related to hair cycle and may also play a critical role in regulating the periodic development of HF.

The epidermal growth factor receptor decreases Stathmin 1 and triggers catagen entry in the mouse.

The epidermal growth factor receptor (EGFR) is necessary for normal involution of hair follicles after the growth phase of anagen, although the mechanisms through which it acts are not well understood. In this report, we used transcriptional profiling of microdissected hair follicles from mice with skin-targeted deletion of Egfr to investigate how EGFR activation triggers catagen. Immunofluorescence for phospho-EGFR in mouse skin revealed increased activation of EGFR in follicular keratinocytes at catagen onset. Consistent with other models of EGFR deficiency, mice with skin-targeted deletion of Egfr (Krt14-Cre(+) /Egfr(fl/fl) ) exhibited a delayed and asynchronous catagen entry. Transcriptional profiling at the time of normal catagen onset at post-natal day (P) 17 revealed increased expression of the mitotic regulator Rcc2 in hair follicles lacking EGFR. Rcc2 protein was strongly immunopositive in the nuclei of control follicular keratinocytes at P16 then rapidly decreased until it was undetectable between P18 and 21. In contrast, Rcc2 expression continued in Egfr mutant follicles throughout this period. Proliferation, measured by bromodeoxyuridine incorporation, was also significantly increased in Egfr mutant follicular keratinocytes compared to controls at P18-21. Similarly, Rcc2-regulated mitotic regulator Stathmin 1 was strikingly reduced in control but not Egfr mutant follicles between P17 and P19. Deletion of Stmn1, in turn, accelerated catagen entry associated with premature cessation of proliferation in the hair follicles. These data reveal EGFR suppression of mitotic regulators including Rcc2 and Stathmin 1 as a mechanism for catagen induction in mouse skin.

Absence of catagen/telogen phase and loss of cytokeratin 15 expression in hair follicles in lichen planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a lymphocyte-mediated cicatricial alopecia mostly involving the bulge region of the hair follicle. The origin of LPP is unknown. Therapy for LPP often does not prevent disease progression. We describe histologic and immunohistologic features that aid in diagnosis and provide an explanation for disease progression in LPP. OBJECTIVE: We sought to demonstrate a decrease in the number of catagen-/telogen-phase follicles and to confirm the loss of cytokeratin 15 (CK15) expression in the stem cells of LPP-affected follicles. METHODS: In all, 144 LPP cases were retrieved; 55 cases were stained immunohistochemically, targeting the CK15 antigen with 40 cases ultimately analyzed for CK15 expression. RESULTS: Catagen/telogen phase was significantly decreased or absent in all cases of LPP, a novel clue useful in histologic diagnostics. The loss of CK15+ stem cells in most affected follicles in LPP was also confirmed, with unaffected follicles retaining CK15+ stem cells. LIMITATIONS: Limited tissue for analysis remained in the clinical sample tissue blocks. CONCLUSION: Damaged follicles that have lost their CK15+ stem cells disappear when they enter catagen phase. CK15+ stem cell loss explains the clinical observation that LPP progresses despite immunosuppressive therapies. Finally, the absence of catagen/telogen hair follicles is a helpful diagnostic clue for LPP.

FGF5 is a crucial regulator of hair length in humans.

Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, we identified distinct pathogenic mutations within fibroblast growth factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of this gene in several additional trichomegaly families identified an additional mutation in FGF5. We further demonstrated that hair fibers from forearms of these patients were significantly longer than hairs from control individuals, with an increased proportion in the growth phase, anagen. Using hair follicle organ cultures, we show that FGF5 induces regression of the human hair follicle. We have identified FGF5 as a crucial regulator of hair growth in humans for the first time, to our knowledge, and uncovered a therapeutic target to selectively regulate eyelash growth.

Expression of sfrp2 is increased in catagen of hair follicles and inhibits keratinocyte proliferation.

BACKGROUND: Hair follicles undergo cycles of repeated growth and regression. The Wnt pathway plays an important role in the regeneration and differentiation of hair follicles. Sfrp2, a Wnt inhibitor, is involved in the developmental and disease processes of various cells and tissues by modulating the Wnt pathway. OBJECTIVE: The aim of this study was to understand the role of Sfrp2 in hair follicles through investigation of the Sfrp2 expression pattern in the skin and its effect on keratinocytes. METHODS: We investigated Sfrp2 mRNA expression and the expression of the wnt target genes, Ccnd1 and C-myc, at various mouse hair follicle developmental stages using Real-time polymerase chain reaction. We also investigated the effect of SFRP2 on the proliferation and differentiation of mouse keratinocyte cells by adding SFRP2 protein or overexpressing Sfrp2 using an in vitro culture system. RESULTS: Sfrp2 expression peaked in the catagen phase and remained high until telogen, and then declined at the beginning of the next anagen. An inverse relationship to Sfrp2 expression was found for the expression of the Wnt target genes, C-myc and Ccnd1. In addition, we also observed inhibited proliferation of mouse keratinocytes in the presence of SFRP2. CONCLUSION: These results suggest that Sfrp2 may play a role in the catagen phase by inhibiting the proliferation of keratinocyte and functioning as a Wnt inhibitor in keratinocytes.