Langton AK, Herrick SE, Headon DJAn extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. J Invest Dermatol 128:1311-1318

Faculty of Life Sciences, University of Manchester, Manchester, UK.
Journal of Investigative Dermatology (Impact Factor: 6.37). 06/2008; 128(5):1311-8. DOI: 10.1038/sj.jid.5701178
Source: PubMed

ABSTRACT Hair follicles have been observed to provide a major cellular contribution to epidermal healing, with emigration of stem-derived cells from the follicles aiding in wound reepithelialization. However, the functional requirements for this hair follicle input are unknown. Here we have characterized the keratinocyte stem cell status of mutant mice that lack all hair follicle development on their tail, and analyzed the consequent alterations in epidermal wound healing rate and mechanisms. In analyzing stem cell behavior in embryonic skin we found that clonogenic keratinocytes are relatively frequent in the ectoderm prior to hair follicle formation. However, their frequency in the interfollicular epidermis drops sharply by birth, at which time the majority of stem cells are present within the hair follicles. We find that in the absence of hair follicles cutaneous wounds heal with an acute delay in reepithelialization. This delay is followed by expansion of the region of activated epidermis, beyond that seen in normal haired skin, followed by appropriate wound closure. JID Journal Club article: for questions, answers, and open discussion about this article please go to

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    • "The fact that PSU-derived cells are detected within the IFE shortly after injury suggests that normal boundaries between the PSU and the IFE do not prohibit cell migration and mixing between compartments following injury (Nowak et al., 2008; Levy et al., 2007). In contrast to full-thickness wounding, cells from within the PSU are not required for tissue repair following incisional wounds in the tail epithelium (Langton et al., 2008), and lineage-tracing data show that IFE-derived progeny in general are a major source for regeneration in response to a small biopsy on the tail (Mascre et al., 2012). It is therefore clear that the severity of the initial trauma greatly influences the regenerative process and the cellular response. "
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    ABSTRACT: The epidermis is an integral part of our largest organ, the skin, and protects us against the hostile environment. It is a highly dynamic tissue that, during normal steady-state conditions, undergoes constant turnover. Multiple stem cell populations residing in autonomously maintained compartments facilitate this task. In this Review, we discuss stem cell behaviour during normal tissue homeostasis, regeneration and disease within the pilosebaceous unit, an integral structure of the epidermis that is responsible for hair growth and lubrication of the epithelium. We provide an up-to-date view of the pilosebaceous unit, encompassing the heterogeneity and plasticity of multiple discrete stem cell populations that are strongly influenced by external cues to maintain their identity and function.
    Development 07/2014; 141(13):2559-2567. DOI:10.1242/dev.104588 · 6.27 Impact Factor
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    • "Compartmentalization IFE SCs have been shown to be the major contributor to tissue regeneration following injury (Mascré et al., 2012); however, evidence from hairless mice and lineage tracing from pilosebaceous SCs supports a role for these cells in the regenerative response (Brownell et al., 2011; Ito et al., 2005; Langton et al., 2008; Snippert et al., 2010). It has also not been clear to what extent cells were specifically retained in the IFE following tissue repair based on their ancestry (Plikus et al., 2012). "
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    ABSTRACT: The complex anatomy of the epidermis contains multiple adult stem cell populations, but the extent to which they functionally overlap during homeostasis, wound healing, and tumor initiation remains poorly defined. Here, we demonstrate that Lrig1(+ve) cells are highly proliferative epidermal stem cells. Long-term clonal analysis reveals that Lrig1(+ve) cells maintain the upper pilosebaceous unit, containing the infundibulum and sebaceous gland as independent compartments, but contribute to neither the hair follicle nor the interfollicular epidermis, which are maintained by distinct stem cell populations. In contrast, upon wounding, stem cell progeny from multiple compartments acquire lineage plasticity and make permanent contributions to regenerating tissue. We further show that oncogene activation in Lrig1(+ve) cells drives hyperplasia but requires auxiliary stimuli for tumor formation. In summary, our data demonstrate that epidermal stem cells are lineage restricted during homeostasis and suggest that compartmentalization may constitute a conserved mechanism underlying epithelial tissue maintenance.
    Cell stem cell 08/2013; 13(4). DOI:10.1016/j.stem.2013.07.010 · 22.15 Impact Factor
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    • "The collaborative effort of the interfollicular and the follicular components of the skin during the re-epithelialization phase are evident by the recent characterization of the hair follicle stem cells as responsible for approximately 25% of cells found in the healed skin (Ito et al, 2005). These cells are essential for the accelerated healing during the initial phase of re-epithelialization (Langton et al, 2008). Underneath the re-epithelialization process, a new wound bed is formed by the migration of newly recruited fibroblasts and endothelial cells along with macrophages that together form the granulation tissue. "
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    ABSTRACT: The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K-PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.
    Oral Diseases 01/2013; 19(6). DOI:10.1111/odi.12070 · 2.40 Impact Factor
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