Dr. Valentina Greco Uncovers the Secrets Behind Skin and Hair Regeneration

Our skin is made up of three layers. The top layer – the epidermis – contains epithelial cells, which provide a barrier between us and the outside world. This part of the skin is in a state of constant turnover— generating and shedding billions of cells each day to replenish its surface.

Underneath this layer is the dermis. Part of the dermis is a network of cells called fibroblasts, which help the skin maintain its structural integrity. This layer of the skin also contains our hair follicles, which package together cells to create hair.

The third layer, which lies beneath the dermis, is the hypodermis. The hypodermis contains fat and connective tissue that act as padding and insulation for the body.

In three recent papers, NYSCF – Robertson Stem Cell Investigator and the Carolyn Walch Slayman Professor of Genetics at Yale University Valentina Greco, PhD, took a closer look at how our skin and hair cells regenerate, as well as how fibroblasts help our skin maintain its structure as we age.

Skin Stem Cells Are Influenced by Their Peers

The first paper, in Cell Stem Cell, asks the question: how do the stem cells in the epidermis stay active throughout a lifetime? Scientists have long thought that the activity of stem cells in the skin served as a catalyst for the activity of cells around them and prompted further renewal, but Dr. Greco’s findings, which examined how this process occurred in mice, suggest the opposite.

“It is what happens in the neighborhood that triggers renewal of stem cells, not renewing stem cells that change the neighborhood,” explains Katie Cockburn, PhD, a postdoctoral researcher in Dr. Greco’s lab and a co-author of the study.

Understanding this process gives us a better idea of how cells interact within the skin, potentially informing new methods for understanding and accelerating wound healing.

Hair Stem Cells Are Flexible

In the second paper, published in Nature Cell Biology, the team explored how stem cells are able to develop into different types of mature, adult cells. They decided to study how this process occurs in mouse hair follicles, where stem cells turn into hair cells.

Again, the researchers tracked the development of single cells within the hair follicle and found that stem cells retain the ability to become other cell types (known as pluripotency) much longer than expected. Even when a stem cell is far down the path to becoming hair, it still has the capacity to become something else.

We know that stem cells can become more flexible (or readier to change identity) upon injury, making it easier for them to help with wound healing, but this study shows that stem cell flexibility can be maintained even in an uninjured state.

Fibroblasts Pick Up the Slack

Unlike epithelial cells, fibroblasts do not move around—they stay rooted in their spots. But as we age, some fibroblasts begin to die, leaving gaps next to their neighbors.

In the lab’s third study, published in Cell, the researchers tracked fibroblast activity in mice and found that when a fibroblast dies, those around it will start to branch out, filling in the empty space and partially compensating for the loss of structure we see in the skin as we get older.

Understanding how loss of structure in the skin occurs—as well as how the body tries to naturally compensate for it—may inform treatments for the effects of aging or the fibroblast malfunction that occurs in fibrosis or cancer.

Looking to the Future

Dr. Greco is excited to continue studying the behavior and interactions of our skin and hair cells.

“Using our imaging techniques, we’ve been able to understand how different cell types implement different strategies to sustain their own tissue types,” says Dr. Greco. “What we are fascinated to understand, moving forward, is how they talk to each other and interact within the organ as a whole, and how the regeneration of our skin and hair is controlled.”