Embryonic stem cells shape the skin’s healing power

Stefania Nicoli, PhD. Photo courtesy Yale School of Medicine

The outer surface of the skin, noted for its regenerative processes, may owe its resilience to lessons learned before birth. In a study published October 10 in Nature Communications, researchers at Yale School of Medicine report that embryonic skin stem cells establish the physical and molecular groundwork that allows the body to repair itself throughout life.

Led by Kaelyn Sumigray, PhD, and Stefania Nicoli, PhD, the team found that in zebrafish embryos—whose skin organization mirrors that of early human development—basal epidermal stem cells (BECs) help form a dual-layered structure essential to healing. By producing and arranging two key extracellular matrix proteins, collagen and laminin, the cells create a balance between stability and flexibility as the embryo grows.

“We were curious how to make skin more resilient to injury,” said Dr. Nicoli, an associate professor of medicine (cardiology) and genetics, in a press release. “We found a mechanism that makes our skin tougher, which is exciting in a sense that it is an overarching concept that could apply across our entire adult body.”

The researchers noted that BECs rich in laminin suppress the formation of desmosomes—protein complexes that fasten neighbouring cells together—loosening cell-to-cell attachments and enabling greater mobility during tissue repair. Conversely, BECs that favour collagen production enhance desmosome formation, reinforcing structural cohesion but limiting regenerative potential. The complementary activity of these two pathways, the scientists conclude, provides embryos both the pliability to grow and the ability to mend quickly.

“The stem cells have a mechanical logic to build a protective layer,” added Dr. Nicoli. “This is the first evidence of this function, which makes us rethink the properties of stem cells.”

In human fetal skin, a similar interplay appears to occur between the temporary outer barrier, the periderm, and the underlying layer of epidermal stem cells. Modelling studies by the Yale group showed that collagen and laminin matrices exert comparable effects on human keratinocytes, with laminin specifically inhibiting desmosome assembly.

“This is the first evidence of this function, which makes us rethink the properties of stem cells,” Dr. Nicoli said, adding that the insights extend beyond dermatology. “Although stem cells are present throughout the adult body, they typically remain dormant. It would be exciting if we could one day guide stem cells to create personalized mechanical shields that protect the tissues where they reside.”

The discovery not only advances understanding of skin biology but also points toward strategies for engineering more resilient grafts and improving regenerative treatments for wound repair and organ transplantation, the researchers say.