Hair Follicle Cycling Research Articles

Elucidation of the Potential Hair Growth-Promoting Effect of Botryococcus terribilis, Its Novel Compound Methylated-Meijicoccene, and C32 Botryococcene on Cultured Hair Follicle Dermal Papilla Cells Using DNA Microarray Gene Expression Analysis.

A person’s quality of life can be adversely affected by hair loss. Microalgae are widely recognized for their abundance and rich functional components. Here, we evaluated the hair growth effect of a green alga, Botryococcus terribilis (B. terribilis), in vitro using hair follicle dermal papilla cells (HFDPCs). We isolated two types of cells from B. terribilis—green and orange cells, obtained from two different culture conditions. Microarray and real time-PCR results revealed that both cell types stimulated the expression of several pathways and genes associated with different aspect of the hair follicle cycle. Additionally, we demonstrated B. terribilis’ effect on collagen and keratin synthesis and inflammation reduction. We successfully isolated a novel compound, methylated-meijicoccene (me-meijicoccene), and C32 botryococcene from B. terribilis to validate their promising effects. Our study revealed that treatment with the two compounds had no cytotoxic effect on HFDPCs and significantly enhanced the gene expression levels of hair growth markers at low concentrations. Our study provides the first evidence of the underlying hair growth promoting effect of B. terribilis and its novel compound, me-meijicoccene, and C32 botryococcene.

Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles.

As one of the main appendages of skin, hair follicles play an important role in the process of skin regeneration. Hair follicle is a tiny organ formed by the interaction between epidermis and dermis, which has complex and fine structure and periodic growth characteristics. The hair growth cycle is divided into three continuous stages, growth (anagen), apoptosis-driven regression (catagen) and relative quiescence (telogen). And The Morphogenesis and cycle of hair follicles are regulated by a variety of signal pathways. When the signal molecules in the pathways are abnormal, it will affect the development and cycle of hair follicles, which will lead to hair follicle-related diseases.This article will review the structure, development, cycle and molecular regulation of hair follicles, in order to provide new ideas for solving diseases and forming functional hair follicle.

Integrated analysis of lncRNAs and mRNAs by RNA-Seq in secondary hair follicle development and cycling (anagen, catagen and telogen) of Jiangnan cashmere goat (Capra hircus).

BackgroundAmong the world’s finest natural fiber composites is derived from the secondary hair follicles (SHFs) of cashmere goats yield one of the world's best natural fibres. Their development and cycling are characterized by photoperiodism with diverse, well-orchestrated stimulatory and inhibitory signals. Long non-coding RNA (lncRNAs) and mRNAs play important roles in hair follicle (HF) development. However, not many studies have explored their specific functions in cashmere development and cycling. This study detected mRNAs and lncRNAs with their candidate genes and related pathways in SHF development and cycling of cashmere goat. We utilized RNA sequencing (RNA-Seq) and bioinformatics analysis on lncRNA and mRNA expressions in goat hair follicles to discover candidate genes and metabolic pathways that could affect development and cycling (anagen, catagen, and telogen).ResultsWe identified 228 differentially expressed (DE) mRNAs and 256 DE lncRNA. For mRNAs, catagen and anagen had 16 upregulated and 35 downregulated DEGs, catagen and telogen had 18 upregulated and 9 downregulated DEGs and telogen and anagen had 52 upregulated and 98 downregulated DEGs. LncRNA witnessed 22 upregulated and 39 downregulated DEGs for catagen and anagen, 36 upregulated and 29 downregulated DEGs for catagen and telogen as well as 66 upregulated and 97 downregulated DEGs for telogen and anagen. Several key genes, including MSTRG.5451.2, MSTRG.45465.3, MSTRG.11609.2, CHST1, SH3BP4, CDKN1A, GAREM1, GSK-3β, DEFB103A KRTAP9–2, YAP1, S100A7A, FA2H, LOC102190037, LOC102179090, LOC102173866, KRT2, KRT39, FAM167A, FAT4 and EGFL6 were shown to be potentially important in hair follicle development and cycling. They were related to, WNT/β-catenin, mTORC1, ERK/MAPK, Hedgehog, TGFβ, NFkB/p38MAPK, caspase-1, and interleukin (IL)-1a signaling pathways.ConclusionThis work adds to existing understanding of the regulation of HF development and cycling in cashmere goats via lncRNAs and mRNAs. It also serves as theoretical foundation for future SHF research in cashmere goats.

Expression of miRNA-1-3p and its target gene in hair follicle cycle development of Liaoning Cashmere goat

MicroRNA exerts an important regulatory role in almost all the biological process, including hair follicle development in Liaoning Cashmere goat. In order to improve the Cashmere performance of goat, the regulatory role of microRNA in hair follicle cycle has drawn hotspot attention. However, the molecular mechanisms of miRNA-1-3p involved in hair follicle development are poorly understood. In this study, we found that miRNA-1-3p was less expressed in anagen stage of hair follicle cycle of Cashmere goat than that in telogen stage by using RT-qPCR and immunoblotting analysis, in contrast to the expression pattern of FGF14. The Dual-Luciferase reporter assay was employed to verify the relationship between miRNA-1-3p and FGF14. The results showed that miRNA-1-3p specifically binds to the 3′UTR of FGF14 mRNA, and FGF14 is the target gene of miR-1-3p. In conclusion, this study shows that miRNA-1-3p may regulate hair follicle development in Liaoning Cashmere goats by targeting FGF14.

Genome-wide identification, characterization, and expression analysis of keratin genes (KRTs) family in yak (Bos grunniens).

As the largest subgroup of intermediate filament proteins, keratins are divided into two types of subfamily. Currently, the molecular mechanism of keratins in several animals has been reported but is limited in yak. Here, 53 different kinds of keratins were identified in the yak genome, including 23 type I and 30 type II keratins. Bioinformatics analysis in this study revealed that multiple phosphorylation sites were identified among all the family members. And the subcellular localization of these proteins was predicted to be in the nucleus, cytoskeleton, and cytoplasm. All keratin family proteins were unstable and the scores of instability coefficient were higher than 40. Phylogenetic analysis showed that high consistency results of the sequence conservation and grouping were found in the genomes of yak, sheep, cattle, mouse, rat, and human. Based on the expression patterns obtained from the transcriptome data, keratin genes (KRTs) were grouped into five clusters, and results also showed that KRTs were highly activated in skin tissues during the hair cycle in yak. Among the five clusters, Cluster II contained the most KRTs, which was the main expression pattern of the yak hair follicle cycle, followed by Cluster III. These results indicated the transition period from telogen to anagen and catagen to telogen were highly dynamic in yak. Gene expression correlation analysis showed that KRTs exhibited a strong correlation (mainly positive correlation) throughout the hair follicle development cycle. And the identification of hub KRTs in specific modules related to hair follicle development in this study was performed using the Weight Gene Co-Expression Network Analysis (WGCNA). Specific modules that include KRTs were darkgreen (KRT40), darkgrey (KRT5), turquoise (KRT1, KRT2, KRT10), bisque4 (KRT4), thistle2 (KRT9, KRT39), and yellowgreen (KRT24). The interaction network showed that these genes were found to be related to the regulation of cell cycle, melanogenesis, hair follicle development, keratinocyte proliferation. Our study provides theoretical support for the study of the evolutionary relationship and molecular mechanism of keratin family in B. grunnien.

Phenotypical Conversions of Dermal Adipocytes as Pathophysiological Steps in Inflammatory Cutaneous Disorders.

Adipocytes from the superficial layer of subcutaneous adipose tissue undergo cyclic de- and re-differentiation, which can significantly influence the development of skin inflammation under different cutaneous conditions. This inflammation can be connected with local loading of the reticular dermis with lipids released due to de-differentiation of adipocytes during the catagen phase of the hair follicle cycle. Alternatively, the inflammation parallels a widespread release of cathelicidin, which typically takes place in the anagen phase (especially in the presence of pathogens). Additionally, trans-differentiation of dermal adipocytes into myofibroblasts, which can occur under some pathological conditions, can be responsible for the development of collateral scarring in acne. Here, we provide an overview of such cellular conversions in the skin and discuss their possible involvement in the pathophysiology of inflammatory skin conditions, such as acne and psoriasis.

Hair Growth-Promoting Activities of Glycosaminoglycans Extracted from the Tunics of Ascidian (Halocynthia roretzi).

Throughout the ages, hair has had psychological and sociological importance in framing the personality and general appearance of an individual. Despite efforts to solve this problem, no groundbreaking measures have been proposed. Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Three fractions (F1, F2 and F3) were obtained after separation and purification of GAGs from ascidian tunics. F1 was observed to contain a small amount of amino sugar while high contents of galactose and N-acetylglucosamine were noted in F2 and F3. 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (∆Di-6S) and 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (∆Di-4S) were the main disaccharide components. F3 exhibited the highest proliferation activity on human follicle dermal papilla (HFDP) cells. In addition, mixed samples (FFM) of F2 and F3 at different concentrations showed peak activities for five days. After cell culture at a concentration of 10 mg/mL and dihydrotestosterone (DHT), the inhibition effect was higher than that for Minoxidil. Application of 10 mg of FFM to the hair of mice for 28 days resulted in a hair growth effect similar to that of Minoxidil, a positive control.

Deletion of hypoxia-inducible factor prolyl 4-hydroxylase 2 in FoxD1-lineage mesenchymal cells leads to congenital truncal alopecia

Hypoxia-inducible factors (HIFs) induce numerous genes regulating oxygen homeostasis. As oxygen sensors of the cells, the HIF prolyl 4-hydroxylases (HIF-P4Hs) regulate the stability of HIFs in an oxygen-dependent manner. During hair follicle (HF) morphogenesis and cycling, the location of dermal papilla (DP) alternates between the dermis and hypodermis and results in varying oxygen levels for the DP cells. These cells are known to express hypoxia-inducible genes, but the role of the hypoxia response pathway in HF development and homeostasis has not been studied. Using conditional gene targeting and analysis of hair morphogenesis, we show here that lack of Hif-p4h-2 in Forkhead box D1 (FoxD1)-lineage mesodermal cells interferes with the normal HF development in mice. FoxD1-lineage cells were found to be mainly mesenchymal cells located in the dermis of truncal skin, including those cells composing the DP of HFs. We found that upon Hif-p4h-2 inactivation, HF development was disturbed during the first catagen leading to formation of epithelial-lined HF cysts filled by unorganized keratins, which eventually manifested as truncal alopecia. Furthermore, the depletion of Hif-p4h-2 led to HIF stabilization and dysregulation of multiple genes involved in keratin formation, HF differentiation, and HIF, transforming growth factor β (TGF-β), and Notch signaling. We hypothesize that the failure of HF cycling is likely to be mechanistically caused by disruption of the interplay of the HIF, TGF-β, and Notch pathways. In summary, we show here for the first time that HIF-P4H-2 function in FoxD1-lineage cells is essential for the normal development and homeostasis of HFs.

Mitochondrially Localized MPZL3 Functions as a Negative Regulator of Sebaceous Gland Size and Sebocyte Proliferation

Mitochondrially localized nucleus-encoded Ig-like v-type protein, MPZL3, regulates lipid metabolism, energy expenditure, as well as epidermal keratinocyte differentiation and function (Bhaduri et al., 2015; Leiva et al., 2014; Wikramanayake et al., 2021). Previous studies have shown increased energy expenditure and insulin sensitivity (Czyzyk et al., 2013), epidermal barrier defects and a seborrheic dermatitis–like inflammatory skin phenotype (Wikramanayake et al., 2017, 2018), as well as altered hair follicle cycling (Nicu et al., 2020) in Mpzl3 global knockout (GKO) (GKO–/–) mice.

Oxidant and antioxidant status in patients with female pattern hair loss with varying severity

Background Female pattern hair loss (FPHL), also known as female androgenic alopecia, is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including FPHL. Aim This study was aimed to investigate the levels of oxidative stress biomarkers in patients with FPHL with varying severities. Patients and methods The study involved 56 patients with FPHL and 46 healthy controls. Diagnosis was based on clinical examination and trichoscopic evaluation. Patients were grouped into three subgroups as follows: mild, moderate, and extensive. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase, total antioxidant capacity, and malondialdehyde (MDA). Results Plasma levels of MDA in FPHL were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes superoxide dismutase and CAT were lower. Moreover, total antioxidant capacity was also low in patients with FPHL as compared with that of the controls. Higher MDA levels in the extensive FPHL subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the extensive FPHL subgroup, a significant negative correlation was observed between MDA and CAT levels. Conclusion The data suggest that oxidative stress plays a key role in FPHL progress, which accelerates hair loss by causing microinflammation and fibrosis. The recognition of the effect of androgens and associated factors on the hair follicle cycle is essential for the development of new and effective treatment methods and may be employed as a biomarker index to assess the disease’s activity and to monitor its treatment.

A Summary of Pre-Clinical and Clinical Evidence for Cannabinoid Hair Follicle Effects

The endocannabinoid system (ECS), discovered in the 1990s, is a system involved with maintaining cellular homoeostasis by down-regulating the damaging inflammatory responses and upregulating regenerative processes. Tetrahydrocannabinol (THC), Cannabidiol (CBD), tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV) are all phytocannabinoids that have novel therapeutic effects on hair growth through the ECS receptors on hair follicles. These cannabinoids are fat-soluble and poorly absorbed past the epidermis, but topical application easily reaches hair follicles where CBDV, THCV and CBD act as partial or full CB1 antagonists and agonists of vanilloid receptor-1 (TRPV1) and vanilloid receptor-4 (TRPV4). All these ECS receptors relate to hair follicle function. THC on the other hand has the opposite effects decreasing hair shaft elongation and matrix production. A summary of the pre-clinical and clinical cannabinoid research is reviewed. The studies confirm that for androgenetic alopecia (AGA) the method of action is different from and synergistic with current hair regrowth therapies. Blocking the CB1 receptor on the hair follicle has been shown to result in hair shaft elongation and matrix production via keratinocytes, in addition, the hair follicle cycle (anagen, catagen, and telogen phases) is controlled by TRPV1. The effects of CBD on hair growth are dose dependent and higher doses may result in premature entry into the catagen phase via a different receptor known as TRPV4. CBD has also been shown to increase Wnt signaling, which causes dermal progenitor cells to differentiate into new hair follicles and maintains anagen phase of the hair cycle. Two recent six-month duration clinical trials of adults with androgenetic alopecia (AGA) have revealed an average 93.5% increased hair count with CBD alone, and 164% increased hair count with hemp extract high in CBD, THCV, CBDV and menthol. A current study is underway to look at punch biopsies of the areas of hair regrowth in patients treated with a combination of CBD, THCV isolate, menthol and caffeine. Another study is underway looking at using hexahydrocannabinol (HHC) a hydrogenated version of THC to decrease facial hair growth as a cosmetic effect

Serum Vitamin B12 in chronic telogen effluvium patients: A case–control study

Background: Diffuse hair loss is a common complaint in dermatology clinics. Chronic telogen effluvium is a common form of diffuse hair loss. Chronic telogen effluvium is characterized usually by the abrupt onset of diffuse shedding of telogen hairs for more than 6 months. Micronutrients such as Vitamin B 12 are major elements in the normal hair follicle cycle. Vitamin B12 levels in chronic telogen effluvium are not well characterized. Purpose: The aim of this study is to compare Vitamin B12 levels in chronic telogen effluvium patients to controls. Methods: A case–control study was conducted in the department of dermatology of a tertiary care hospital; a total of 70 patients were included, 35 in each group. Results: Twenty-five(71%) chronic telogen effluvium patients were females; 60% had Vitamin B12 deficiency (<250 pg/ml). In controls, fewer (26%) subjects had Vitamin B12 deficiency (P = 0.004). Conclusion: As per our study, Vitamin B12 deficiency was more common in patients with telogen effluvium than in controls.

Identification of the Key Genes Associated with the Yak Hair Follicle Cycle.

The development of hair follicles in yak shows significant seasonal cycles. In our previous research, transcriptome data including mRNAs and lncRNAs in five stages during the yak hair follicles (HFs) cycle were detected, but their regulation network and the hub genes in different periods are yet to be explored. This study aimed to screen and identify the hub genes during yak HFs cycle by constructing a mRNA-lncRNA co-expression network. A total of 5000 differently expressed mRNA (DEMs) and 729 differently expressed long noncoding RNA (DELs) were used to construct the co-expression network, based on weighted genes co-expression network analysis (WGCNA). Four temporally specific modules were considered to be significantly associated with the HFs cycle of yak. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the modules are enriched into Wnt, EMC-receptor interaction, PI3K-Akt, focal adhesion pathways, and so on. The hub genes, such as FER, ELMO1, PCOLCE, and HOXC13, were screened in different modules. Five hub genes (WNT5A, HOXC13, DLX3, FOXN1, and OVOL1) and part of key lncRNAs were identified for specific expression in skin tissue. Furthermore, immunofluorescence staining and Western blotting results showed that the expression location and abundance of DLX3 and OVOL1 are changed following the process of the HFs cycle, which further demonstrated that these two hub genes may play important roles in HFs development.

Deficiency of Formyl Peptide Receptor 2 Retards Hair Regeneration by Modulating the Activation of Hair Follicle Stem Cells and Dermal Papilla Cells in Mice.

Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient's psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.

Ligand-Independent Actions of the Vitamin D Receptor: More Questions Than Answers.

ABSTRACTOur predominant understanding of the actions of vitamin D involve binding of its ligand, 1,25(OH)D, to the vitamin D receptor (VDR), which for its genomic actions binds to discrete regions of its target genes called vitamin D response elements. However, chromatin immunoprecipitation‐sequencing (ChIP‐seq) studies have observed that the VDR can bind to many sites in the genome without its ligand. The number of such sites and how much they coincide with sites that also bind the liganded VDR vary from cell to cell, with the keratinocyte from the skin having the greatest overlap and the intestinal epithelial cell having the least. What is the purpose of the unliganded VDR? In this review, I will focus on two clear examples in which the unliganded VDR plays a role. The best example is that of hair follicle cycling. Hair follicle cycling does not need 1,25(OH)2D, and Vdr lacking the ability to bind 1,25(OH)2D can restore hair follicle cycling in mice otherwise lacking Vdr. This is not true for other functions of VDR such as intestinal calcium transport. Tumor formation in the skin after UVB radiation or the application of chemical carcinogens also appears to be at least partially independent of 1,25(OH)2D in that Vdr null mice develop such tumors after these challenges, but mice lacking Cyp27b1, the enzyme producing 1,25(OH)2D, do not. Examples in other tissues emerge when studies comparing Vdr null and Cyp27b1 null mice are compared, demonstrating a more severe phenotype with respect to bone mineral homeostasis in the Cyp27b1 null mouse, suggesting a repressor function for VDR. This review will examine potential mechanisms for these ligand‐independent actions of VDR, but as the title indicates, there are more questions than answers with respect to this role of VDR. © 2021 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Skin aging: Dermal adipocytes metabolically reprogram dermal fibroblasts.

Emerging data connects the aging process in dermal fibroblasts with metabolic reprogramming, provided by enhanced fatty acid oxidation and reduced glycolysis. This switch may be caused by a significant expansion of the dermal white adipose tissue (dWAT) layer in aged, hair-covered skin. Dermal adipocytes cycle through de-differentiation and re-differentiation. As a result, there is a strongly enhanced release of free fatty acids into the extracellular space during the de-differentiation of dermal adipocytes in the catagen phase of the hair follicle cycle. Both caveolin-1 and adiponectin are critical factors influencing these processes. Controlling the expression levels of these two factors also offers the ability to manipulate the metabolic preferences of the different cell types within the microenvironment of the skin, including dermal fibroblasts. Differential expression of adiponectin and caveolin-1 in the various cell types may also be responsible for the cellular metabolic heterogeneity within the cells of the skin.

NEDD4-1 Is a Key Regulator of Epidermal Homeostasis and Wound Repair

The ubiquitin ligase NEDD4-1 plays key roles in organ development, tissue homeostasis, and cancer, but its functions in the skin are largely unknown. In this study, we show perturbations in keratinocyte (KC) proliferation and terminal differentiation, epidermal barrier function, and hair follicle cycling as well as increased UV-induced apoptosis in mice lacking NEDD4-1 in KCs. In particular, re-epithelialization of full-thickness excisional wounds was delayed in the mutant mice. This was caused by severely impaired migration and proliferation of NEDD4-1‒deficient KCs. Therefore, a few KCs, which had escaped recombination and expressed NEDD4-1, obtained a growth advantage and contributed to re-epithelialization. Mechanistically, NEDD4-1‒deficient KCs failed to efficiently activate the extracellular signal-regulated kinase 1/2/MAPKs and the YAP transcriptional coactivator. These results identify NEDD4-1 as an essential player in wound repair through its effect on mitogenic and motogenic signaling pathways in KCs.

321 Deletion of hypoxia-inducible factor prolyl 4-hydroxylase 2 in FoxD1-lineage mesenchymal cells leads to congenital truncal alopecia

We aimed to investigate how the depletion of hypoxia inducible factor prolyl-4 hydroxylase 2 (HIF- P4H-2) in Forkhead Box D1 (FoxD1) lineage cells affects hair follicle (HF) and skin development. Hypoxia-inducible factors (HIFs) induce hundreds of genes regulating oxygen homeostasis in tissues. The HIF-P4Hs regulate the stability and hence the activity of HIFs in an oxygen-dependent manner. The skin is a hypoxic organ with endogenous HIF expression but the role of hypoxia signalling in skin and HFs are poorly understood. We studied a mouse line where Hif-p4h-2 is conditionally inactivated in FoxD1-expressing (FoxD1+) cells. This mouseline was studied at different developmental stages during the HF morphogenesis and cycle. To be able to pinpoint the location of FoxD1+ cells we studied the skin of a mouse line where FoxD1+ cells could be seen due to the expression of enhanced green fluorescent protein and the non-FoxD1-expressing cells due to the expression of tomato-red. Lack of Hif-p4h-2 in FoxD1-lineage mesodermal cells causes disturbed HF development during the first catagen leading to formation of large epithelial lined HF cysts filled with keratins, which eventually manifests as truncal alopecia. The cranial hair remains normal. We show that FoxD1+ cells are mesenchymal cells located in the dermis and dermal papilla of truncal skin. FoxD1+ cells are scarce in the cranial skin. The depletion of Hif-p4h-2 in FoxD1+ cells misregulates genes crucial for hypoxia response, keratin formation and differentiation, TGF-β and Notch signalling pathways, which are known to be essential for the HF development and cycling. We show here for the first time that HIF-P4H-2 function in FoxD1-lineage cells is essential for the normal development and homeostasis of HFs.

323 Human Long-Term Deregulated Circadian Rhythm Alters Regernerative Properties of Skin and Hair Precursor Cells

In mammals, desynchronized circadian rhythm leads to various biological symptoms. In skin and hair, human epidermal stem cell function in vitro is regulated by circadian oscillations, and thus contributes to tissue aging when deregulated. In mice, circadian arrhythmia of hair follicle stem cells contributes to age-related hair follicle cycling defects. Despite the well-described impact of circadian oscillations through a feedback loop involving the clock pathway on hair and skin stem cell function in vitro, little is known about the change in characteristics or regenerative properties of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) after long-term alteration of circadian rhythm in vivo. The present study was designed to asses hHF, hEpi, and hHFDP precursors and stem cell properties in response to clock pathway alteration due to long-term deregulated circadian rhythm in vivo. A clinical study protocol involving two groups of women was designed: diurnal workers (control) and shift workers (deregulated). After informed consent, two 3-mm fresh punch biopsies were taken from the occipital region of each donor (10 donors/group). Cell culture characterization, measurement of colony area, culture medium analysis, and RT -qPCR analysis were carried out. Long-term circadian rhythm deregulation affected clock pathway protein expression and correlated with alterations in hHF, hEpi, and hHFDP properties. This study provides evidence that in vivo deregulation of the clock pathway affects regenerative properties of human skin and hair precursor cells.

078 Treatment of hereditary hypotrichosis simplex of the scalp with topical gentamicin

Hypotrichosis simplex of the scalp (HSS) is characterized by progressive loss of scalp hair at a young age with often devastating psychological implications for affected children. HSS is often caused by dominant nonsense variants in CDSN encoding corneodesmosin. The resulting mutant protein leads to the formation of an amyloid like material, which interferes with normal hair follicle cycle. Decreasing the level of the mutant protein is therefore expected to result in a clinically beneficial effect.