What’s new in hair — March 2017 | Dr. Yuval Ramot

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

Nat Commun. 2017 Mar 8;8:14694. doi: 10.1038/ncomms14694

Male pattern baldness (MPB) has a very strong genetic basis, as has been proven by several genetic studies. In this study, Heilmann-Heimbach et al. performed a meta-analysis of eight independent genome-wide association studies (GWAS) samples, incorporating more than 20,000 samples (10,846 early-onset MPB cases, 11,672 controls). This is largest GWAS meta-analysis of MPB to date. Sixty-three genome-wide significant MPB-risk loci were identified. Some of the MPB-risk loci identified confirm previous associations (e.g. the AR/EDA2R-locus on Xq12); however, 23 of these loci have not been reported previously. A pathway-based analysis found involvement of new possible mechanisms that are involved in MPB, such as melatonin signalling/degradation, adipogenesis and immune related pathways. When the data from this meta-analysis were compared to reported GWAS signals from the NHGRI GWAS catalogue, the association between MPB and prostate cancer could be confirmed. This study gives further support to the notion that MPB is not an isolated trait, and shares a biological basis with several other human phenotypes. The information provided by this study provides new therapeutic targets for MPB.

 

Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients

J Am Acad Dermatol. 2017 Mar 8. pii: S0190-9622(16)31288-9. doi: 10.1016/j.jaad.2016.12.027. [Epub ahead of print]

More than half of the patients treated with chemotherapy suffer from anagen effluvium, which leads to a significant psychological effect on the patients. In a subset of breast cancer patients, permanent alopecia has been reported. In this study, Fonia et al. describe 10 breast cancer patients that developed permanent alopecia following treatment with taxanes and adjuvant hormonal therapy. They observed 3 patterns of scalp alopecia: diffuse alopecia with only sparse hair; diffuse alopecia with accentuation on the vertex of the scalp; and diffuse and patchy alopecia. Histopathologically, all the patients had features consistent with advanced/end-stage permanent alopecia, which can also be observed in androgenic alopecia and alopecia areata. The authors suggest a “dual target” hypothesis, in which the hair bulb is the first target, resulting from direct effect of chemotherapy, with the residual hair follicle being the second target, resulting from the antiestrogen hormonal adjuvant therapy. This study calls for a more extensive clinicopathologic evaluation of patients undergoing chemotherapy to better understand the morphobiologic timeframe of permanent alopecia development.

 

Alopecia areata

Nat Rev Dis Primers. 2017 Mar 16;3:17011. doi: 10.1038/nrdp.2017.11.

After a very long period of “walking in the dark”, there is great advancement in recent years in our understanding of the pathogenesis of alopecia areata, leading to the emergence of new treatment modalities. In this manuscript, Pratt et al. provide a comprehensive review on the disease, highlighting the recent advancements in the pathogenesis and treatment options. This review is accompanied by very helpful summarizing boxes and figures, which help to better understand the complex mechanism that underlies this disease. This review is an invaluable source for people interested in this disease, and provides an updated overview of the different aspects relating to this condition.

 

The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine

ACS Biomater. Sci. 2017 March 21. DOI: 10.1021/acsbiomaterials.7b00072

The hair follicle is the only organ in adult humans, other than the mammary gland, that is capable of degeneration and regeneration. Therefore, it is an invaluable source for the research of regenerative medicine. In this article, Kiani et al. provide a very comprehensive review of the regenerative capabilities of the hair follicle. They provide examples of how the hair follicle can influence skin regeneration, such as in the process of wound healing, and focus on the compartments within the hair follicle that harbour cells that can be utilized in regenerative medicine, such as the bulge and the mesenchymal dermal papilla and sheath. Cells from the hair follicle possess low immunogenicity, are easy to access, and differentiate efficiently. Indeed, trials in humans are underway using dermal sheath cells to treat chronic Achilles tendinosis and bulge cells are utilized for the treatment of chronic ulcers. Furthermore, keratin, the major component of the hair fiber, which provides strength and resilience, is highlighted in this review as a source for biomaterial in regenerative medicine. Overall, this interesting review underlines an important aspect of the hair follicle, which has not been sufficiently explored by the scientific community.

 

Macrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF

Nat Commun. 2017 Mar 27;8:14091. doi: 10.1038/ncomms14091

Macrophages are important in creating a regenerative environment in injured tissues, including skin wounds. They are also important in hair follicle regeneration and wound-induced hair growth. In this study, Wang et al. have used two genetic mice models to evaluate the role of Ly6C+ inflammatory macrophages and CX3CR1+ tissue-resident macrophages in wound-induced hair anagen re-entry/growth and wound-induced hair follicle neogenesis. They show that in both models, TNF played an important role in these processes. TNF works by inducing AKT phosphorylation in epidermal stem cells and Lgr5+ cells, which in turn regulates β-catenin signalling. These observations highlight the importance of TNF after wounding in inducing hair follicle regeneration, and show that major players in this process are the hair follicle stem cells.

 

Compartmentation of Mitochondrial and Oxidative Metabolism in Growing Hair Follicles: A Ring of Fire

J Invest Dermatol. 2017 Mar 23. pii: S0022-202X(17)31309-X. doi: 10.1016/j.jid.2017.02.983. [Epub ahead of print]

The hair follicle epithelial cells are among the most-proliferating cells in the body. Cell proliferation and the hair shaft elongation are energized by glycolysis, but mitochondrial metabolism also takes a role in this process. In this study, Lemasters et al. utilized the novel technology of multiphoton and light-sheet microscopy of parameter-indicating fluorophores to assess the intrafollicular distribution of mitochondrial and oxidative metabolism of anagen hair follicles from bovine and human sources. The results were surprising, showing that in different follicular compartments there are gradients of mitochondrial and oxidative metabolism. There was pronounced mitochondrial hyperpolarization and ROS formation in a paraxial circumferential ring within the follicle, associated with the formation of the hair cuticle and outer cortex, termed by the authors “the ring of fire”. This is the first time that multiphoton and light-sheet microscopy are used to evaluate the compartmentation of hair follicle metabolic activity, showing that the pick energetic activity is located at the interface between viable matrix epidermal cells and the newly forming hair shaft.

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