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No description available.

Female ageing leads to reduced hair density and thinner fibres. The impact of the ageing dermal environment on the hair follicles (HFs) remains unclear. This study documents in situ changes in human female scalp skin of women (19-81 years (yrs)), and corresponding primary cultures of dermal fibroblast (DF) and dermal sheath (DS) cells. In situ, the papillary/reticular boundary was indistinguishable in young scalp, but delineated over 40yrs, with reduced rete ridges, changes in collagen organisation, reduced podoplanin (PDPN) and increased versican (VCAN) expression. Hyaluronic acid synthase 2 (HAS2) was highly expressed throughout the scalp. Matrix Metallopeptidase 1 (MMP1) and Metallopeptidase inhibitor 1 (TIMP1), cyclin-dependent kinase inhibitor 2A (p16INK4A), 11β-Hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1/HSD11B1 and 11β-HSD2/HSD11B2) mRNA expression increased in aged DFs. In DS cells, HAS2, Vimentin (VIM) ,PDPN, Lysosomal-associated membrane protein 1 (LAMP1), Sequestosome- 1 (P62) and Protease nexin-1 (SERPINE2) increased, while α-smooth muscle actin (aSMA) decreased. Both cell types exhibited elevated cartilage oligomeric protein (COMP) mRNA expression. Proteomics revealed elevated COMP expression in the DF secretome with age, suggesting a more fibrotic phenotype or DS migration into the dermis. DF and DS lysate protein expression suggests altered extracellular matrix (ECM) remodelling due to increased levels of MMP-2 and Protease inhibitor Plasminogen activator inhibitor-1 (Serpin E1/PAI-1). Cathepsin C/DPPI protein lysate expression decreased in DFs but increased in DS. In summary, ageing female scalp shows striking structural and biological changes in the HF environment that may impact hair growth, due to alterations in ECM, senescence and autophagy associated biomarkers.

Epigenetic mechanisms play an important role during the morphogenesis of the hair follicle and the hair cycle. Work on hair regeneration is of importance as no products are available which can provide complete reversal of hair loss. Tet2 promotes DNA demethylation by the hydroxylation of 5mC to 5hmC which in turn causes gene transcription activation. Dermal papilla (DP) cells located within the hair follicle are responsible for the regulation of development and the growth of hair follicles. Fgf20 signalling controls commitment of the mesenchymal precursor cells to the DP progenitor lineage. An immature DP cells is then formed during maturation by Shh signalling which then stimulates these to differentiate into a DP cell by BMP and Wnt signalling. Methylated DNA can be bound by the proteins recruiting transcription corepressors. DNA methyltransferases (DNMT’s) can be degraded by decitabine which reverses gene silencing. Conditional knockout of Tet2 in mouse DP cells results in a delay in anagen initiation, suggesting Tet2 is involved in the telogen-anagen transition. Additionally, by using dermal fibroblasts and RA-DPAC (Dermal Papilla activating medium supplemented with retinoic acid), it was found that decitabine can increase plasticity in dermal fibroblasts and RA-DPAC can be used to accelerate a lineage change to DP cells which is supported by the significant increase in the DP specific gene expression. Examples include AlPl, LEF1, BMP4/6/7, FGF10, BMPR1A and PDGFA. Additionally, by way of siRNA and conditional Tet2 knockout data in dermal fibroblasts, it was found Tet2 regulates signature DP genes such as Bmpr1a, ALPL, Tcf4 and SOX2.

No / Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction of cAMP with up-regulation of pro-opiomelanocortin gene expression and subsequent production of adrenocorticotropin hormone. However, the role of CRH/CRH-R in melanocyte biology is complicated by the significant heterogeneity of cutaneous melanocyte subpopulations, from continuously active and UV-responsive melanocytes in epidermis to UV nonresponsive, hair growth cycle-coupled melanogenesis in hair follicles. In the present study we report that normal human scalp hair follicle melanocytes express CRH at the mRNA level. Furthermore, CRH, urocortin and CRH-R 1 and 2 were differentially expressed in follicular melanocytes, fibroblasts, and keratinocytes depending on anatomic location and differentiation status in situ and in vitro. Stimulation of follicular melanocytes with CRH and CRH peptides, modified for selectivity for CRH-R1 and/or CRH-R2, variably induced cell melanogenesis, dendricity, and proliferation. CRH-peptides also stimulated the expression and activity of Tyrosinase, and expression of Tyrosinase-related protein-1 and-2. However, a modified urocortin peptide highly selective for CRH-R2 down-regulated melanocyte differentiation phenotype. This study indicates that CRH peptides can differentially influence hair follicle melanocyte behavior not only via CRH-R1 signaling but also by complex cross-talk between CRH-R1 and CRH-R2.¿Kauser, S., Slominski, A., Wei, E. T., Tobin, D. J. Modulation of the human hair follicle pigmentary unit by corticotropin-releasing hormone and urocortin peptides.

No / The hair shaft has increasing importance in bioarchaeology, since it is now possible to retrieve detailed biomolecular information on recent life history using individual fibres (e.g., on diet, drug use and DNA). Data on hair condition is an important cornerstone to ensuring that reliable information is obtained. The following study defines morphological features of degradative change in human terminal scalp hair using different microscopy techniques. Evidence of degradative change is translated into a ranked histology for assessing hair sample condition. The approach is applied to samples of cut modern scalp hair subjected to degradation under soil burial/simulated grave conditions.

No / The hair follicle is a cyclic biological system that progresses through stages of growth, regression, and quiescence, which involves dynamic changes in a program of gene regulation. Micro-RNAs (miRNAs) are critically important for the control of gene expression and silencing. Here, we show that global miRNA expression in the skin markedly changes during distinct stages of the hair cycle in mice. Furthermore, we show that expression of miR-31 markedly increases during anagen and decreases during catagen and telogen. Administration of antisense miR-31 inhibitor into mouse skin during the early- and midanagen phases of the hair cycle results in accelerated anagen development, and altered differentiation of hair matrix keratinocytes and hair shaft formation. Microarray, qRT-PCR and Western blot analyses revealed that miR-31 negatively regulates expression of Fgf10, the components of Wnt and BMP signaling pathways Sclerostin and BAMBI, and Dlx3 transcription factor, as well as selected keratin genes, both in vitro and in vivo. Using luciferase reporter assay, we show that Krt16, Krt17, Dlx3, and Fgf10 serve as direct miR-31 targets. Thus, by targeting a number of growth regulatory molecules and cytoskeletal proteins, miR-31 is involved in establishing an optimal balance of gene expression in the hair follicle required for its proper growth and hair fiber formation.

No / P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. As patients with mutations in the gene that encodes P-cadherin show hypotrichosis and fair hair, we explored the hypothesis that P-cadherin may control HF pigmentation. When P-cadherin was silenced in melanogenically active organ-cultured human scalp HFs, this significantly reduced HF melanogenesis and tyrosinase activity as well as gene and/or protein expression of gp100, stem cell factor, c-Kit, and microphthalmia-associated transcription factor (MITF), both in situ and in isolated human HF melanocytes. Instead, epidermal pigmentation was unaffected by P-cadherin knockdown in organ-cultured human skin. In hair matrix keratinocytes, P-cadherin silencing reduced plasma membrane β-catenin, whereas glycogen synthase kinase 3 beta (GSK3β) and phospho-β-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3β/Wnt signaling is required for maintaining the expression of MITF to sustain intrafollicular melanogenesis. Thus, P-cadherin-mediated signaling is a melanocyte subtype-specific topobiological regulator of normal human pigmentation, possibly via GSK3β-mediated canonical Wnt signaling.

No / Although we have made significant progress in understanding the regulation of the UVR-exposed epidermal-melanin unit, we know relatively little about how human hair follicle pigmentation is regulated. Progress has been hampered by gaps in our knowledge of the hair growth cycle’s controls, to which hair pigmentation appears tightly coupled. However, pigment cell researchers may have overly focused on the follicular melanocytes of the nocturnal and UVR-shy mouse as a proxy for human epidermal melanocytes. Here, I emphasize the epidermis-follicular melanocyte pluralism of human skin, as research models for vitiligo, alopecia areata and melanoma, personal care/cosmetics innovation. Further motivation could be in finding answers to why hair follicle and epidermal pigmentary units remain broadly distinct? Why melanomas tend to originate from epidermal rather than follicular melanocytes? Why multiple follicular melanocyte sub-populations exist? Why follicular melanocytes are more sensitive to aging influences? In this perspective, I attempt to raise the status of the human hair follicle melanocyte and highlight some species-specific issues involved which the general reader of the pigmentation literature (with its substantial mouse-based data) may not fully appreciate.