To achieve regeneration without scarring is an important goal in the medical research community. Some species are capable of proficient regeneration of even whole limbs or internal organs, but mammalian regeneration is stunted by comparison, sidetracked into the process of scar formation. This is likely a side-effect of processes that act to reduce cancer incidence, but researchers have not yet achieved a sufficiently comprehensive understanding of regeneration in species with different capabilities to be certain. Here, researchers note a demonstration of skin regeneration without scarring, produced by upregulation of the lef1 transcription factor. Studies of this nature can help to focus scientific investigations into more productive directions, narrowing down areas of interest in the cellular biochemistry of regeneration.

Researchers have identified a factor that acts like a molecular switch in the skin of baby mice that controls the formation of hair follicles as they develop during the first week of life. The switch is mostly turned off after skin forms and remains off in adult tissue. When it was activated in specialized cells in adult mice, their skin was able to heal wounds without scarring. The reformed skin even included fur and could make goose bumps, an ability that is lost in adult human scars.

Researchers used a new technique called single cell RNA sequencing to compare genes and cells in developing skin and adult skin. In developing skin, they found a transcription factor – proteins that bind to DNA and can influence whether genes are turned on or off. The factor the researchers identified, called Lef1, was associated with papillary fibroblasts which are developing cells in the papillary dermis, a layer of skin just below the surface that gives skin its tension and youthful appearance.

When the researchers activated the Lef1 factor in specialized compartments of adult mouse skin, it enhanced the skins’ ability to regenerate wounds with reduced scarring, even growing new hair follicles that could make goose bumps. Researchers first got the idea to look at early stages of mammalian life for the capacity to repair skin because after emergency life-saving surgery in utero, it was observed that when the babies were born they did not have any scars from the surgery. A lot of work still needs to be done before this latest discovery in mice can be applied to human skin, but it is an important advance.