Despite the success of epidermal stem cell therapy, many questions remain on their true potency in steady state conditions. Indeed, the maintenance of the interfollicular epidermis (IFE) remains a controversial subject. Conflicting studies support the existence a stem cell hierarchy in the IFE or a committed progenitor (CP) activity without a specific hierarchy. We generated transgenic mice containing a Brainbow-1.0 cassette allowing the random expression of different fluorescent proteins upon cre recombination. When crossed with K14-Cre/ER transgenic mice, this allowed us to induce recombination in all basal keratinocytes regardless of their anatomical location and to follow their fate over time.
Clones within the IFE of dorsal skin grew in size from 3 to 24 weeks (p<0.001) in accordance with the committed progenitor model. Analysis of clone size relative to their positioning revealed that clones that were attached or contained a hair follicle were significantly larger (p<0.05) and grew more steadily overtime (p<0.0001) especially during active hair cycling.
We proposed a model where stem cell populations in HF generated CPs around them which behaved with random fate decision. Using this model, computer simulations integrating 6 colour staining and animal growth predicted clone sizes that closely matched our observations.
In conclusions, Rainbow technology allows the long term tracking of clones derived from individual stem cells. Our results support a hierarchical contribution of upper hair follicle stem cells to dorsal IFE by differentiating into committed progenitors.