May 2024
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38 Reads
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1 Citation
Developmental Biology
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May 2024
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38 Reads
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1 Citation
Developmental Biology
May 2024
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12 Reads
Journal of Investigative Dermatology
September 2023
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28 Reads
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1 Citation
Journal of Investigative Dermatology
April 2023
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419 Reads
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60 Citations
Nature
For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations¹, which leads to hair greying in most humans and mice2,3. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli4–8. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.
March 2023
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12 Reads
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2 Citations
Cell
No two fingerprint patterns are exactly alike. In this issue of Cell, Glover et al. uncover the molecular and cellular mechanisms that result in patterned skin ridges over volar digits. This study reveals that the remarkable diversity of fingerprint configurations may originate from a common patterning code.
October 2022
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50 Reads
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15 Citations
Journal of Investigative Dermatology
Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new hair follicles regenerate in the center of large full-thickness wounds of mice in a process called wound-induced hair neogenesis (WIHN). WIHN is followed by neogenesis of dermal adipose tissue. Both neogenic events reactivate embryonic-like cellular and molecular programs. The WIHN model provides a platform for studying mammalian regeneration, and findings from this model could instruct future regenerative medicine interventions for treating wounds and alopecia. Since Ito et al. rediscovered WIHN 15 years ago, numerous investigators have worked on the WIHN model using varying wounding protocols and model interpretations. Because a variety of factors, including environmental variables and choice of mouse strains, can affect the outcomes of a WIHN study, the purpose of this article is to provide an overview of the experimental variables that impact WIHN so that experiments between laboratories can be compared in a meaningful manner.
July 2022
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96 Reads
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3 Citations
Nature Aging
The microenvironment can regulate adult stem cell function during tissue homeostasis and regeneration, but whether and how this is altered in aging is unclear. Ichijo et al. find that increased dermal stiffness, as a result of vasculature atrophy, activates cation channel PIEZO1, leading to interfollicular epidermal stem cell dysregulation.
May 2021
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23 Reads
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2 Citations
Nature Cell Biology
The distribution of skin immune cells, namely Langerhans cells (LCs) and dendritic epidermal T cells (DETCs), is well-documented, but the mechanisms underlying their pattern maintenance remained obscure. A study now finds that LCs maintain their distribution patterns depending upon Rac1 and that the density of LCs and DETCs is regulated by the density of epithelial cells.
March 2020
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495 Reads
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87 Citations
Science Advances
Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.
December 2019
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16 Reads
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1 Citation
Cell Stem Cell
Hair follicle stem cells may themselves regulate the niche environment for hair follicle regrowth. A recent Science paper from Elaine Fuchs and colleagues (Gur-Cohen et al., 2019) suggests that this involves regulation of the lymphatic system and may have implications in understanding tissue regeneration.
... This tool helps clarify the molecular mechanisms underlying the transition of hair follicle stem cells from the telogen to anagen phase and explores Krt24's role in this pro-cess. Additionally, this model can be crossed with reporter mice (such as Rosa26 LSL-tdTomato , Rosa26 LSL-DTR ) to perform lineage-tracing of quiescent bulge HFSCs in hair follicle regeneration and wound repair and further reveal their differentiation potential [34,[46][47][48]. Furthermore, this model has the application potential to study how abnormal function of bulge HFSCs leads to hair follicle atrophy or regenerative disorders [35,49], and to study the role of bulge HFSCs in skin tumors [50,51]. ...
April 2023
Nature
... Clinical application of WIHN has been difficult due to the lack of dermal γδ T cells in human scalps [30], but drug development including Wnt signaling activators is increasing the effectiveness of WIHN in humans [17,43]. Translational studies using various animal models have also made important contributions to the development of potential drugs to induce WIHN in humans [48]. Importantly, the development of these drugs for practical and clinical purposes may provide many opportunities to treat alopecia. ...
October 2022
Journal of Investigative Dermatology
... Distribusi sel imun kulit yaitu sel Langerhans (LCs) dan sel T epidermal dendritik (DETCs), terdokumentasi dengan baik, tetapi mekanisme yang mendasari pemeliharaan pola mereka tetap tidak jelas. Sebuah studi sekarang menemukan bahwa LC mempertahankan pola distribusinya tergantung pada Rac1 dan bahwa kepadatan LC dan DETC adalah diatur oleh kepadatan sel epitel 36 . Kulit mewakili organ dalam dan dunia luar. ...
May 2021
Nature Cell Biology
... The WNT ligand secreted by bulge ESCs activates the proliferation of dermal fibroblasts and formation of DP. However, chronic WNT signaling, stimulated by phagocytosis of the WNT inhibitor SFRP4 by macrophages, is implicated in uncontrolled fibrosis in HS (Gay et al, 2020). DP cells secrete local extracellular vesicles that induce ESC to regenerate the hair follicle through the nonconventional WNT ligand norrin (le Riche et al, 2019), whereas clathrinmediated endocytosis, implicated in the uptake of exosomes, has recently been identified as induced in the tunnel epidermis (Adawi et al, 2025). ...
March 2020
Science Advances
... Clusters with fewer than 50 cells were excluded, resulting in a final count of 2776 cells distributed across 10 clusters. As the number of clusters obtained was larger than that obtained in the original study which produced the dataset (Sun et al. 2019), we merged related clusters to create more coarse-grained groupings. The original study performed . ...
Reference:
Pseudoassembly of k-mers
November 2019
... The WIHN is a regenerative phenomenon that can be exploited in the treatment of alopecia and is regulated by various factors [3,8]. In particular, the WIHN is mainly regulated by the following three factors. ...
November 2018
... McSCs are critical for pigmented hair-follicle regeneration [26][27][28][29]. McSCs migrate from the hair-follicle niche to the epidermis after wounding and contribute to the generation of unpigmented hairs in the wounds [26]. ...
February 2018
Journal of Investigative Dermatology
... In compliance with the guidelines established by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, measures were taken to minimize the number of animals used in this study, with the goal of reducing both the number of animals and the associated suffering. In line with the 3Rs principle�replace, reduce, and refine�the number of rats (3 to 5 rats per time point) was determined based on prior studies, 6,24,32,35,36 while three rabbits per test group were deemed adequate for a comprehensive assessment of dermal irritation. 33,37 Female rodents typically show faster wound healing due to the role of 17β-estradiol in enhancing A2A adenosine receptormediated angiogenesis through estrogen receptors and vascular endothelial growth factor (VEGF). ...
January 2018
Journal of Investigative Dermatology
... Abnormal skin scaring has significantly threatened the health of hundreds of millions of patients, forcing us to develop timely and effective treatment methods [1][2][3]. Keloids, which are tumor-like scars with fibroproliferative and exophytic outgrowing characteristics, can not only cause pruritus and pain but also lead to aesthetic damage and dysfunction [4]. They are easy to occur by abnormally wound healing after injury and even a minor trauma or infection, which however are very difficult to treat and ready to recur due to the unclear etiology and pathogenesis [5,6]. ...
January 2017
Science
... McSCs are critical for pigmented hair-follicle regeneration [26][27][28][29]. McSCs migrate from the hair-follicle niche to the epidermis after wounding and contribute to the generation of unpigmented hairs in the wounds [26]. ...
April 2016
Cell Reports