Clone size evolution in the interfollicular epidermis is bimodal and regulated by hair follicles and their cycling

K Khosrotehrani

The University of Queensland

Interfollicular epidermal (IFE) homeostasis is a major physiological process that allows the maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We used multi-colour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones. Two modes of clonal progression could be observed. Clones attached to hair follicles showed rapid increase in size during the growth phase of the hair cycle. On the other hand clones distant from hair follicles were slow-cycling as they retained DNA labels long term, but could be mobilized by a proliferative stimulus. Reinforced by mathematical modelling, these data support a model where progenitor cycling characteristics are differentially regulated in areas surrounding or away from growing hair follicles. Thus, while IFE progenitors follow a non-hierarchical mode of development, spatiotemporal control by their environment can change their potentialities, with far reaching implications in our understanding of epidermal homeostasis, wound repair and cancer development.