Skin is an excellent tool to study the onset of cancer since the epidermis of the skin is one of the best-studied stem cell systems and cancer is believed to arise from deregulated stem cell populations. Epidermal stem cells are located in distinct niches of the hair follicle, the sebaceous gland and the interfollicular epidermis and their respective progeny are restricted to defined areas. However, injuries like acute wounds disturb the balance of homeostasis and allow stem cell progeny to repopulate new areas. Cancer also disturbs – or needs a disturbed – homeostasis, thus it is not surprising that wound healing and cancer are tightly linked processes.
In order to build a comprehensive picture of skin cancer initiation we will:
A. Determine the cellular contribution of the different stem cells in epidermal homeostasis, and investigate the ability of a wound to reprogram stem cells.
B. Construct a single-cell resolution 3D hair follicle map.
C. Investigate the roles of distinct stem cell niches in tumorigenesis.
D. Uncover the molecular and epigenetic regulation of stem cells, regenerative wound-front cells and newly transformed cancer-initiating cells.
The proposed research will for the first time generate a complete map of a functional mammalian organ at single cell resolution, unravel the level of stem cell diversity and plasticity, and reveal how wound healing and stem cell reprogramming influence skin cancer development.