Browsing by Author "Hagner, Andrew"

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    Characterizing the cellular diversity and molecular signatures within the hair follicle dermal stem cell lineage
    (2017) Hagner, Andrew; Biernaskie, Jeff; Cobb, John; Dobrinski, Ina; Kurrasch, Debbie
    Mammalian skin is capable of tissue repair upon injury, but is unable to perform true, scarless regeneration in all but the most superficial of injuries. Consequently, many injuries form scar tissue, an excessive deposition of cross-linked collagen that suffers from poor elasticity, reduced resistance to ultraviolet radiation, and an absence of hair and sweat glands that regulate skin function. Fibroblasts, the progeny of mesenchymal stem cells of the dermis, are the source of scar tissue. Fibroblasts themselves are essential for the proper function of many tissues in the body, particularly in a supportive role for all epithelia, such as the skin, lung and intestine (Di Wang et al., 2010). The dysfunction of skin fibroblasts is of particular clinical importance to problems with wound healing, fibrosis, hair loss, and skin aging. Fibroblasts are a highly plastic cell type, capable of a wide array of functions, yet we have only begun to appreciate their diversity (Driskell et al., 2013). Furthermore, we have only recently discovered the existence of a hair follicle-associated dermal stem cell (hfDSC), and a comprehensive characterization of hfDSCs and their progeny is lacking (Rahmani et al., 2014). To explore tissue regeneration and perhaps develop new wound-healing strategies, an understanding of the molecular signaling governing adult dermal fibroblast behavior must be achieved, so that fibroblast behavior can be coopted or controlled. This thesis is therefore concerned with developing a strategy to specifically isolate adult hfDSCs and their progeny, to discern which molecular controls are involved in generating different types of skin fibroblasts, and to investigate the reciprocal signaling used by mesenchymal cells to modulate epithelial cell function during regeneration. Using a novel FACS strategy to isolate adult hfDSCs/progeny from adult skin at the onset of HF regeneration, I performed RNA-seq to establish gene expression signatures for specialized fibroblasts of the HF, and tested Rspo2/3, Grem2 and Hic1, signature genes that I found to control fibroblast function. Taken together, my research identifies unique transcriptional programs that underlie the functional heterogeneity amongst specialized fibroblasts within the adult hair follicle, and furthers our understanding of mesenchymal cell contribution to tissue regeneration.