Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin

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Abstract Highly regenerative tissues such as blood and skin may utilize blood vessels as dual players in tissue growth functions: one in supplying O2/nutrients and another in regulating tissue stem cell activity via signaling. Correlative evidence suggest that skin endothelial cells may act as signaling niches to adult hair follicle stem cells (HFSCs), regulating their quiescence. To demonstrate this, we need gene targeting of signaling molecules in endothelial cells that in turn would affect stem cell activity. Furthermore, recent work on skin vasculature probed a role of lymphatic vessels but not of blood vessels in adult HFSC activation. Finally, the extent of skin vasculature remodeling and its genetic control during the hair cycle are poorly understood. We propose to use a combined genetic and genomic approach in mice to address all these questions. Our mouse models provide an exciting entry point to address the cross- communication of HFSCs with the neighboring endothelial cells, to probe its physiological relevance, and to place endothelial cells for the first time as bona-fide signaling niches for adult HFSCs. This work will have future broad relevance for human skin regeneration studies and for more in depth understanding of skin vasculature disease.