title: Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling.
abstract: 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.
authors: UQ Centre for Clinical Research, Experimental Dermatology Group, The University of Queensland, Brisbane, Qld, Australia.
authors: Edwige
authors: 0000-0003-1991-5844
authors: E
authors: Roy
authors: School of Mathematics and Physics, The University of Queensland, Brisbane, Qld, Australia.
authors: Zoltan
authors: Z
authors: Neufeld
authors: School of Mathematics and Physics, The University of Queensland, Brisbane, Qld, Australia.
authors: Luca
authors: L
authors: Cerone
authors: UQ Centre for Clinical Research, Experimental Dermatology Group, The University of Queensland, Brisbane, Qld, Australia.
authors: Ho Yi
authors: HY
authors: Wong
authors: UQ Centre for Clinical Research, Experimental Dermatology Group, The University of Queensland, Brisbane, Qld, Australia.
authors: Samantha
authors: S
authors: Hodgson
authors: Sorbonne Universités, INSERM, CNRS, Institut de la Vision UPMC Univ Paris 06, Paris, France.
authors: Jean
authors: J
authors: Livet
authors: UQ Centre for Clinical Research, Experimental Dermatology Group, The University of Queensland, Brisbane, Qld, Australia k.khosrotehrani@uq.edu.au.|UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, Qld, Australia.
authors: Kiarash
authors: K
authors: Khosrotehrani
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003584:Cytological Techniques; D000078404:Epidermal Cells; D018859:Hair Follicle / Q000166:cytology*; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D008962:Models, Theoretical; D012867:Skin / Q000166:cytology; D062211:Spatio-Temporal Analysis; D013234:Stem Cells / Q000502:physiology*
keywords: Brainbow model; epidermal stem cells; hair follicle cycle; homeostasis; multicolour tracing model