Mapping the skin in time and space
The skin is the largest organ in mammals and it serves to protect the body from outside influences, such as physical damage, radiation, fluid loss or extreme temperatures. To fulfill this function, a plethora of cell types with diverse functions and molecular identities has to work in concert. However, it is still unclear how many different cell populations can actually be found in the epidermis and the hair follicles, and what exactly makes one cell different from another. In a new study from Karolinska Institutet, researchers provide an in-depth analysis revealing 25 epidermal cell populations that, surprisingly, can be explained almost fully by just two biological parameters - the differentiation status of the cell and the niche in which the cell is located.
The study, a collaboration between the labs of Maria Kasper and Sten Linnarsson, used single-cell RNA-sequencing to analyze the gene expression of more than a thousand individual cells from adult mouse skin. With this method they were able to link each cell to a specific molecular identity and to cluster them accordingly. Analyzing the gene expression signatures associated with each of these cell populations revealed putative functional roles for each population and made it possible to search for shared patterns of gene expression between different populations. These new insights into the organization of the epidermis have profound influence on the understanding of how the skin functions.
"Overall, we were able to find 25 cell populations with distinct molecular identities and functional roles in the murine epidermis and the hair follicle, many of which have not been described before. What was most intriguing was that, despite this high number of different populations and identities, most variety of the cells could be explained by only two parameters – time and space," says the study's first author Simon Joost.
The time parameter would correspond to the differentiation status of the cells – whether they are young and dividing cells in the basal layer, or functionally mature cells in the outer layers. Space would correspond to the niche that the cell is located in – whether they are located in the interfollicular epidermis (the part of the skin that is not hair follicle) where they form the skin barrier, or whether they are located in one of the many compartments of the hair follicle where they grow and maintain the hair.
Furthermore, the study leader Maria Kasper explains, "A vast number of tissue stem cell populations with different gene expression profiles and diverse localizations have been described in the epidermis in recent years. However, our data show that, while the expression profiles of the different populations indeed vary according to their locations, the gene expression linked to their stem cell identity is surprisingly similar across these locations". These findings challenge previous paradigms of skin maintenance.
Understanding the identity and interplay of different cell populations in the healthy skin will enable researchers to better understand the specific changes occurring in skin stem cells, for example when they contribute to wound healing or when they undergo transformation to give rise to a tumor. Thus, this cell map of healthy skin will also benefit future studies on damaged as well as diseased skin.