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Hearing Research Sep 2023Inner ear hair cells assemble mechanosensitive hair bundles on their apical surface that transduce sounds and accelerations. Each hair bundle is comprised of ∼ 100... (Review)
Review
Inner ear hair cells assemble mechanosensitive hair bundles on their apical surface that transduce sounds and accelerations. Each hair bundle is comprised of ∼ 100 individual stereocilia that are arranged into rows of increasing height and width; their specific and precise architecture being necessary for mechanoelectrical transduction (MET). The actin cytoskeleton is fundamental to establishing this architecture, not only by forming the structural scaffold shaping each stereocilium, but also by composing rootlets and the cuticular plate that together provide a stable foundation supporting each stereocilium. In concert with the actin cytoskeleton, a large assortment of actin-binding proteins (ABPs) function to cross-link actin filaments into specific topologies, as well as control actin filament growth, severing, and capping. These processes are individually critical for sensory transduction and are all disrupted in hereditary forms of human hearing loss. In this review, we provide an overview of actin-based structures in the hair bundle and the molecules contributing to their assembly and functional properties. We also highlight recent advances in mechanisms driving stereocilia elongation and how these processes are tuned by MET.
Topics: Humans; Hair Cells, Auditory; Actin Cytoskeleton; Deafness; Hair Cells, Auditory, Inner; Actins; Stereocilia
PubMed: 37300948
DOI: 10.1016/j.heares.2023.108817 -
Indian Journal of Dermatology,... 2023The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata... (Review)
Review
The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata and a potential target for therapy. Here, we give a narrative review of what is known about Janus kinase inhibitors in alopecia areata. Several clinical trials as well as smaller studies have demonstrated hair regrowth and remission with oral Janus kinase inhibitors therapy, even in patients who failed conventional treatment. Baricitinib is the only US FDA-approved treatment for alopecia areata but data for other oral Janus kinase inhibitors such as tofacitinib, ruxolitinib and ritlecitinib are also promising. Fewer clinical trials have investigated topical Janus kinase inhibitors for alopecia areata, with many of them terminated early due to unfavourable results. Overall, Janus kinase inhibitors are an efficacious addition to the therapeutic arsenal for treatment-refractory alopecia areata. Further work is needed to examine the effects of long-term usage of Janus kinase inhibitors, the efficacy of topical Janus kinase inhibitors, as well as to identify biomarkers that could predict differential therapeutic responses to the various Janus kinase inhibitors.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Alopecia; Hair; Janus Kinases
PubMed: 37436019
DOI: 10.25259/IJDVL_1093_2022 -
Stem Cell Reviews and Reports Aug 2023Androgenetic alopecia is the most common cause of hair loss aggravated by increased life pressure, tension, and anxiety. Although androgenetic alopecia (AGA) does not... (Review)
Review
Androgenetic alopecia is the most common cause of hair loss aggravated by increased life pressure, tension, and anxiety. Although androgenetic alopecia (AGA) does not significantly effect physical health, it can have serious negative impact on the mental health and quality of life of the patient. Currently, the effect of medical treatment for AGA is not idealistic, stem cell-based regenerative medicine has shown potential for hair regrowth and follicle repair, but the long-term effect and mechanism of stem cell therapy is not quite explicit. In this review, we summarize the methods, efficacy, mechanism, and clinical progress of stem cell therapies for AGA by now, hope it will present a more comprehensive view in this topic.
Topics: Humans; Quality of Life; Alopecia; Hair; Cell- and Tissue-Based Therapy; Stem Cells
PubMed: 37277541
DOI: 10.1007/s12015-023-10532-2 -
Experimental & Molecular Medicine Feb 2024Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The... (Review)
Review
Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The crucial function of hair follicle stem cells is to maintain these hair growth cycles. Another vital aspect is the activity of melanocyte stem cells, which differentiate into melanin-producing melanocytes, contributing to skin and hair pigmentation. Sebaceous gland stem cells also have a pivotal role in maintaining the skin barrier by regenerating mature sebocytes. These stem cells are maintained in a specialized microenvironment or niche and are regulated by internal and external signals, determining their dynamic behaviors in homeostasis and hair follicle regeneration. The activity of these stem cells is tightly controlled by various factors secreted by the niche components around the hair follicles, as well as immune-mediated damage signals, aging, metabolic status, and stress. In this study, we review these diverse stem cell regulatory and related molecular mechanisms of hair regeneration and disease conditions. Molecular insights would provide new perspectives on the disease mechanisms as well as hair and skin disorder treatment.
Topics: Animals; Hair Follicle; Hair; Skin; Melanocytes; Stem Cells; Mammals
PubMed: 38182654
DOI: 10.1038/s12276-023-01151-5 -
Cell Reports Jun 2023Morphogenesis of ectodermal organs, such as hair, tooth, and mammary gland, starts with the formation of local epithelial thickenings, or placodes, but it remains to be...
Morphogenesis of ectodermal organs, such as hair, tooth, and mammary gland, starts with the formation of local epithelial thickenings, or placodes, but it remains to be determined how distinct cell types and differentiation programs are established during ontogeny. Here, we use bulk and single-cell transcriptomics and pseudotime modeling to address these questions in developing hair follicles and epidermis and produce a comprehensive transcriptomic profile of cellular populations in the hair placode and interplacodal epithelium. We report previously unknown cell populations and marker genes, including early suprabasal and genuine interfollicular basal markers, and propose the identity of suprabasal progenitors. By uncovering four different hair placode cell populations organized in three spatially distinct areas, with fine gene expression gradients between them, we posit early biases in cell fate establishment. This work is accompanied by a readily accessible online tool to stimulate further research on skin appendages and their progenitors.
Topics: Mice; Animals; Hair Follicle; Transcriptome; Mice, Transgenic; Epidermis; Hair
PubMed: 37318953
DOI: 10.1016/j.celrep.2023.112643 -
Nature Communications Aug 2023While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the...
While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the stem-cell niche. Here we use the hair follicle to show that during growth, the mesenchymal niche of the hair follicle, the dermal papilla (DP), is maintained quiescent by the activity of Hdac1 and Hdac2 in the DP that suppresses the expression of cell-cycle genes. Furthermore, Hdac1 and Hdac2 in the DP promote the survival of DP cells throughout the hair cycle. While during growth and regression this includes downregulation of p53 activity and the control of p53-independent programs, during quiescence, this predominantly involves p53-independent mechanisms. Remarkably, Hdac1 and Hdac2 in the DP during the growth phase also participate in orchestrating the hair cycle clock by maintaining physiological levels of Wnt signaling in the vicinity of the DP. Our findings not only provide insight into the molecular mechanism that sustains the function of the stem-cell niche in a persistently changing microenvironment, but also unveil that the same mechanism provides a molecular toolbox allowing the DP to affect and fine tune the microenvironment.
Topics: Hair Follicle; Tumor Suppressor Protein p53; Wnt Signaling Pathway; Stem Cells; Cell Division
PubMed: 37563109
DOI: 10.1038/s41467-023-40573-7 -
Neuroscience Bulletin Jan 2024Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main... (Review)
Review
Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Topics: Infant, Newborn; Humans; Hair Cells, Auditory, Inner; Ear, Inner; Hair Cells, Auditory; Regeneration; Stem Cells
PubMed: 37787875
DOI: 10.1007/s12264-023-01130-w -
Science Immunology Jan 2024Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is...
Immune tolerance is maintained in lymphoid organs (LOs). Despite the presence of complex immune cell networks in non-LOs, it is unknown whether self-tolerance is maintained in these tissues. We developed a technique to restrict genetic recombination to regulatory T cells (T) only in skin. Selective depletion of skin T resulted in T cell-mediated inflammation of hair follicles (HFs). Suppression did not rely on CTLA-4, but instead on high-affinity interleukin-2 (IL-2) receptor expression by skin T, functioning exclusively in a cell-extrinsic manner. In a novel model of HF stem cell (HFSC)-driven autoimmunity, we reveal that skin T immunologically protect the HFSC niche. Finally, we used spatial transcriptomics to identify aberrant IL-2 signaling at stromal-HF interfaces in a rare form of human alopecia characterized by HFSC destruction and alopecia areata. Collectively, these results reveal the fundamental biology of T in skin uncoupled from the systemic pool and elucidate a mechanism of self-tolerance.
Topics: Humans; Immune Privilege; T-Lymphocytes, Regulatory; Hair Follicle; Interleukin-2; Stem Cell Niche
PubMed: 38181095
DOI: 10.1126/sciimmunol.adh0152 -
International Journal of Women's... Oct 2023Alopecia is among the leading dermatological concerns affecting Black women. For many women, hair is a central component of identity and self-expression, the loss of... (Review)
Review
Alopecia is among the leading dermatological concerns affecting Black women. For many women, hair is a central component of identity and self-expression, the loss of which can have significant psychosocial effects. Hair camouflage is often utilized to minimize the visibility of hair loss, provide aesthetic benefits, and improve quality of life. The versatility and affordability of hair camouflage allows patients with alopecia to conceal hair loss, increasing self-confidence, and decreasing social stigma. However, hair camouflage practices often involve adhesives, chemicals, and/or high-tension braiding, all of which can exacerbate alopecia. Accordingly, special considerations should be made to protect patients' natural hair from damage while using these styling practices. A better understanding of best practices for some of the most widely used camouflage options-wigs, extensions, topical hair fibers, and micropigmentation-can help clinicians establish rapport with Black women and optimize individually-tailored therapeutic plans during active treatment and end-stage hair loss.
PubMed: 37799136
DOI: 10.1097/JW9.0000000000000111