Epidermal renewal, which is important for skin barrier function, is characterised by the division and differentiation of cells in the basal layer. However, the properties and heterogeneity of these proliferative cells remain unclear. Here, Tudorita Tumbar and colleagues identify for the first time in vivo, in the mice epidermis, a long-hypothesized population of biphasic non-self-renewing transit-amplifying cells that behaves differently from stem cells. First, from single-cell RNA sequencing analysis, the authors find that Aspm marks a subset of highly proliferative basal progenitors. Genetic lineage tracing confirms that these progenitors contribute to epidermis homeostasis and injury repair. Then, to study the self-renewal behaviour of epidermal cells, the authors label and track clones from single basal layer cells over 1 year. They develop a mathematical model based on long-term lineage tracing data of the Aspm-marked progenitors. The model allows the analysis of biphasic populations in which behaviour changes over time. Clonal analysis suggests that the Aspm-marked cells exhibit biphasic behaviour: they initially divide and amplify the progenitor cell numbers during the growth phase, and then transition to an extinction phase, when cell progeny are all gradually lost from the tissue. Overall, this study contributes to the understanding of cell fate decisions and epidermal renewal.
