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Baldness jokes aside, hair growth is a surprisingly complicated process; follicle formation relies on an intricate, synchronized process of cell migration, and postnatal follicular function requires maintenance of the stem cell population that drives hair formation and growth. The mesenchymal cells of the dermal papilla (DP), residing at the base of the follicle, have long been recognized as being responsible for niche maintenance, although the specifics of this process are poorly understood. Surgical isolation of DP cells is difficult, owing to the follicle's small size and the variety of other cell types closely surrounding the DP, and even successfully isolated DP cells rapidly lose their in vivo properties in culture. As a result, current gene expression data for DP cells is scant—and potentially suspect.

Elaine Fuchs' laboratory at Rockefeller University has long been interested in the processes of hair and skin formation and maintenance, and recently developed an inventive solution to the DP problem. They began by crossing two transgenic mouse lines—one expressing green fluorescent protein (GFP) exclusively in skin epithelium, and the other specifically expressing red fluorescent protein (RFP) in the DP and melanocytes—to generate a strain expressing both fluorescent tags (Fig. 1). Starting with a follicular homogenate derived from mouse backskins, the researchers were thus able to efficiently purify individual cell types via fluorescence-activated cell sorting (FACS), using surface antigens and GFP or RFP expression as indicators.

Figure 1: Section of a hair follicle.
figure 1

This section was taken from a GFP+ (green; epithelial cells) and RFP+ (red; dermal papilla cells and melanocytes) double transgenic mouse after counterstaining with tyrosinase antibodies (blue; melanocytes). Image courtesy of Michael Rendl and PLoS Biology.

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Fuchs' group confirmed the identity and purity of their cell populations and demonstrated that grafts containing keratinocytes and their purified DP cells were capable of generating haired skin on the backs of nude mouse recipients. They then proceeded to conduct an exhaustive series of gene expression profiling experiments on each of their purified cell populations, data that they analyzed closely in hopes of getting new insights into follicle function. “What was really nice about this whole system was that there are closely interacting cell types right next to each other,” explains lead author Michael Rendl, “but getting all of them out in a pure form to define what is very specific to each of them and define what is common to them—that was not done before.”

They established two categories of genes: 'backbone' genes common to each purified cell type, and 'signature' genes that are dramatically upregulated only in individual cell types. These signatures offered a treasure trove of cell type–specific expression data for a wide variety of signaling factors and genes previously linked with hair formation, as well as seve- ral previously unknown genes, and Rendl believes that this information could reveal the communication processes by which the DP collaborates with other cells to maintain the follicle. “There's something very unique about the dermal papilla, because it can induce hair formation,” he says. “The dermal papilla are considered to be mesenchymal cells, like fibroblasts. The question is, what makes the dermal papilla cells special so that they can do that, compared to regular fibroblasts in the skin or other tissues... we basically want to tackle the whole idea of why it's inductive.”