Defining stem cell dynamics and migration during wound healing in mouse skin epidermis

Wound healing is essential to repair the skin after injury. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. However, how SCs balance proliferation, differentiation and migration to repair a wound remains poorly understood. Here we show the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, we identify the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound. Functional experiments show that SC proliferation, migration and differentiation can be uncoupled during wound healing. Lineage tracing and quantitative clonal analysis reveal that, following wounding, progenitors divide more rapidly, but conserve their homeostatic mode of division, leading to their rapid depletion whereas SCs become active, giving rise to new progenitors that expand and repair the wound. These results have important implications for tissue regeneration, acute and chronic wound disorders. To micro dissect the different regions surrounding the wound, at D4 and D7 post wound, one punch of 4mm in diameter was done, around the wound 3mm in diameter, to remove the leading edge zone and a punch of 6mm of diameter was used to remove the proliferative hub. Another piece of skin was taken, as control, from a region far from the wounded area. The two replicates samples at each time point were a pull of 5 CD1 mice. For each sample, 300 basal cells were FACS sorted and used for RNA extraction and hybridization on Affymetrix microarrays.