Skin stem cells give birth to daughter cells that eventually become specialized cells to form our protective, watertight skin and to produce hair. An imbalance of cell type composition, molecular signaling, or stem cell fate decision often results in disease, including cancer and impaired wound healing. With this research program we aim to uncover mechanisms that control stem cells to either self-renew (remain a stem cell) or to differentiate (develop into a specialized skin cell). Building upon the single-cell characterization of skin cell types and their genetic programs from my laboratory, we will investigate how skin-resident immune cells regulate stem cell behavior, and if metabolic changes within a skin stem cell changes its decision to specialize. Based on our previous finding on how to induce new hair follicles in adult mouse skin, we also will work towards a viable strategy for inducing new hair follicles in human skin, a treatment option that is entirely lacking and of worldwide importance for patients with skin-replacement needs. Taken together, with this research program we will determine the boundary to stem cell plasticity and reversibility, with the long-term aim to re-activate skin stem cells in a controlled manner.