Advances in resolving the heterogeneity and dynamics of keratinocyte differentiation

The mammalian skin is equipped with a highly dynamic stratified epithelium. The maintenance and regeneration of this epithelium is supported by basally located keratinocytes, which display stem cell properties, including lifelong proliferative potential and the ability to undergo diverse differentiation trajectories. Keratinocytes support not just the surface of the skin, called the epidermis, but also a range of ectodermal structures including hair follicles, sebaceous glands, and sweat glands. Recent studies have shed light on the hitherto underappreciated heterogeneity of keratinocytes by employing state-of-the-art imaging technologies and single-cell genomic approaches. In this mini review, we highlight major recent discoveries that illuminate the dynamics and cellular mechanisms that govern keratinocyte differentiation in the live mammalian skin and discuss the broader implications of these findings for our understanding of epithelial and stem cell biology in general.