Epidermal Stem Cell Maturation and Lineage Commitment

Cancer Research United Kingdom, London

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Abstract

DESCRIPTION (provided by applicant): The epidermis is continually shed and replenished throughout life. Maintenance of the epidermis is dependent on a stem cell population found in the basal layer of the epidermis. These stem cells self-renew and contribute progenitors called transit amplifying cells. Stem cells and the subsequent transit amplifying cells contribute to multiple lineages of terminally differentiated cells including hair follicle cells, sebocytes, and interfollicular epidermal cells. Although it is clear that epidermal stem cells contribute to all three lineages, the role of transit amplifying cells in lineage commitment remains unknown and largely uninvestigated. The purpose of this proposal is to use in vitro and in vivo methods to investigate if transit amplifying cells contribute to one or multiple lineages. Specifically, the aims are to determine if human neonatal foreskin cultures can make sebocytes and hair follicle proteins, and to use this system to investigate the lineages that develop from a single transit amplifying cell. Additionally, the role of c-Myc and 13-catenin in lineage commitment of transit amplifying cells will be investigated, and using the BOLAP retroviral library, the fate of transit amplifying cells in vivo will be mapped. The process of stem cell maturation is essential to maintain the skin, and disruptions in the stem cell differentiation process have pathological implications in cancer, psoriasis, acne, and hair loss.