Hair Follicle Morphogenesis: Stem Cell Activation and Cell Fate Specification by Dermal Papilla Cells.

    Cell communication between tissue stem cells and their cellular microenvironment within so-called stem cell niches is critical for stem cell self-renewal, differentiation and thus overall tissue homeostasis. But how these specialized niche cells acquire their inductive properties generally remains unknown. The focus of the lab is to understand the general molecular mechanisms of niche cell fate specification that is required for stem cell activation and tissue formation. We use hair follicle development as an attractive model system where a stem cell niche is formed when specialized mesenchymal cells, called dermal papilla (DP) cells, send cues to multipotent long-lived epithelial stem cells, thereby regulating their proliferation and progenitor cell fate, both during embryonic follicle morphogenesis and during adult follicle regeneration (Fig. 1).

Figure 1. Cell communication (black arrows) between epithelial stem cells (SC), progeny and dermal papilla (DP) cells occurs throughout hair follicle development and regeneration.

    We have recently developed transgenic mice that enabled us to isolate pure DP cells and to characterize their molecular signature. Cell fate manipulation either by cytokine activation in vitro or by DP-specific gene ablation in a novel in vitro/in vivo hybrid knockout assay then allowed us for the first time to functionally assess their stem cell-activating, hair inducing properties. We found that Bmp signaling is important for regulating the molecular identity of DP cells in vitro and their hair inducing activity in vivo.

Figure 2. DP cell-specific ablation of Bmpr1a decreases hair formation. Bmpr1a knockout and control DP cells were grafted with keratinocytes onto the backs of Nude mice. Left: Side view of graft area after 3 weeks (macro). Right: Hematoxylin/eosin (H+E) staining of graft samples. Arrowheads point to few aberrant downgrowths.

    The goal now is to systematically employ the established tools to identify the specific molecular events that specify DP character that is crucial for regulating epithelial stem cells. These experiments will identify key mechanisms in the formation of the hair follicle stem cell niche. Such insights will also advance our understanding of other developmental systems where mesenchymal-epithelial communication takes place within a stem cell microenvironment. In addition, these studies could lead to therapeutic strategies to regenerate hair and other tissues.

© 2008 Mount Sinai Medical Center