Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing 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 here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones. Two modes of clonal progression could be observed in the adult murine dorsal skin. 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, 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 for epidermal homeostasis, wound repair and cancer development.
Transgenic lineage tracing and mathematical modelling identify two distinct clonal categories of progenitor cells in the adult epidermis that differ in proliferation and growth, depending on relative hair follicle position and cycle phase.
Clones of epidermal cells that maintain the interfollicular epidermis display bimodal size evolution, stable‐and‐small versus growing.
Growing clones are attached to hair follicles and highly proliferative during the anagen phase.
Small clones are distant from hair follicles and harbour slow‐cycling cells.
Small clones are not influenced by hair cycling, but can be activated in response to strong proliferative signals such as phorbol esters.
At homeostasis, the skin surface covered by each clone type is stable over time.
- Received January 6, 2016.
- Revision received September 23, 2016.
- Accepted September 27, 2016.
- © 2016 The Authors