Our skin rapidly heals our wounds to prevent exposure from infectious microorganisms, but it comes with a price – scars. For example, the hair follicles – the foundations of hair growth in the skin – do not develop completely after serious wounds, leaving visible marks. 

Surprisingly, human fetal skin can regenerate without scars, but we somehow lose this power as we age. Now, scientists found a gene expressed by a specific cell type in the deeper layers in the skin of newborns that supports scar-free regeneration after wounds.

To identify the cell types and molecular factors that guide scar-free skin regeneration, scientists looked at changes in gene expression in the skin of newborn and older mice at single-cell resolution (because mice skin is structurally similar to us). They found different kinds of cells in their analysis. One cell type called fibroblasts caught their eye; these cells are known to support the wound healing process. Although fibroblasts were present in both newborns and older mice, scientists found that fibroblasts from newborns could support the regeneration of hair follicles during the wound healing process. Therefore, they figured that newborns have a special type of fibroblasts that can support scar-free skin regeneration.

They were able to pinpoint the changes in the way genes worked in these special fibroblasts, and a gene called Lef1 stood out. Then, they genetically manipulated older mice to specifically turn on Lef1 levels in the skin fibroblasts. Now backed by the Lef1, fibroblasts of the older skin were able to form hair follicles. Also, the skin regenerated at the wounded area without scars. 

Scientists suggest that Lef1 could relay external cellular signals during early development (like in fetuses). Hence, they are now trying to understand what exactly Lef1 is doing in the fibroblasts. They openly shared the genomic data in an interactive website and hope to “develop clinically tractable solutions that promote the regeneration of adult tissue.”