Extracellular Caspase-1 induces hair stem cell migration in wounded and inflamed skin conditions.

The wound-healing process is a paradigm of the directed migration of various pools of stem cells from their niche to the site of injury where they replenish damaged cells. Two decades have elapsed since the observation that wounding activates multipotent hair follicle stem cells to infiltrate the epidermis, but the cues that coax these cells out of their niche remain unknown. Here, we report that Caspase-1, a protein classically known as an integral component of the cytosolic inflammasome, is secreted upon wounding and has a non-canonical role in the extracellular milieu. Through its caspase activation recruitment domain (CARD), Caspase-1 is sufficient to initiate the migration of hair follicle stem cells into the epidermis. Uncovering this novel function of Caspase-1 also facilitates a deeper understanding of the mechanistic basis of the epithelial hyperplasia found to accompany numerous inflammatory skin diseases.

Approaches to Study Wound-Induced Hair Neogenesis (WIHN).

Embryonic wound repair proceeds with complete regeneration of the tissue without any scar formation, whereas tissue repair in adults usually results in scars and the tissue does not completely regain its preinjured state. Wound-induced hair neogenesis (WIHN) in adult rodents results in de novo hair follicle formation in the center of large wounds, mimicking regeneration processes seen in fetal tissue. The investigation of WIHN therefore provides a unique quantitative framework for scrutinizing the mechanistic underpinnings of regenerative repair, which can have clinical implications in the context of scarless healing. In this chapter, we present a detailed protocol for inducing wounds that lead to hair neogenesis in laboratory mice and facilitating the identification and characterization of distinct stages in neogenic hair follicle development. Additionally, we present a whole-mount alkaline phosphatase assay to distinguish de novo hair follicles. These protocols can facilitate studies toward obtaining a comprehensive understanding of WIHN and shedding light on the intricate molecular and cellular processes involved in mammalian regenerative repair.

Interactions Between Epidermal Keratinocytes, Dendritic Epidermal T-Cells, and Hair Follicle Stem Cells.

The interplay of immune cells and stem cells in maintaining skin homeostasis and repair is an exciting new frontier in cutaneous biology. With the growing appreciation of the importance of this new crosstalk comes the requirement of methods to interrogate the molecular underpinnings of these leukocyte-stem cell interactions. Here we describe how a combination of FACS, cellular coculture assays, and conditioned media treatments can be utilized to advance our understanding of this emerging area of intercellular communication between immune cells and stem cells.

Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells.

The cutaneous wound-healing program is a product of a complex interplay among diverse cell types within the skin. One fundamental process that is mediated by these reciprocal interactions is the mobilization of local stem cell pools to promote tissue regeneration and repair. Using the ablation of epidermal caspase-8 as a model of wound healing in Mus musculus, we analyzed the signaling components responsible for epithelial stem cell proliferation. We found that IL-1α and IL-7 secreted from keratinocytes work in tandem to expand the activated population of resident epidermal γδT-cells. A downstream effect of activated γδT-cells is the preferential proliferation of hair follicle stem cells. By contrast, IL-1α-dependent stimulation of dermal fibroblasts optimally stimulates epidermal stem cell proliferation. These findings provide new mechanistic insights into the regulation and function of epidermal cell-immune cell interactions and into how components that are classically associated with inflammation can differentially influence distinct stem cell niches within a tissue.

Advances in therapies and scope for personalized medicine in Alzheimer's disease.

Alzheimer's disease is one of the leading causes of death worldwide and currently does not have any cure. The rate of incidence of Alzheimer's from 2010 is up by 71%, whereas many other diseases have been decreasing in their prevalence. In this review, we have attempted to cover the current landscape of treatment alongside forthcoming advances. We have also covered the present genes identified through genome-wide association studies, which could be used as novel biomarkers and could eventually reduce the cost of treatment through early diagnosis. As this disease is highly polymorphic, applications of personalized medicine have also found its way. All these upcoming developments offer a bright hope in the diagnosis and treatment of this disease.