Dynamics of Lgr6⁺ progenitor populations in skin

The dynamics and interactions between stem cell pools in the hair follicle (HF), sebaceous gland (SG), and interfollicular epidermis (IFE) of murine skin are still poorly understood. In this study, we used multicolor lineage tracing to mark Lgr6-expressing basal cells in the HF isthmus, SG, and IFE. We show that these Lgr6⁺ cells constitute long-term self-renewing populations within each compartment in adult skin. Quantitative analysis of clonal dynamics revealed that the Lgr6⁺ progenitor cells compete neutrally in the IFE, isthmus, and SG, indicating population asymmetry as the underlying mode of tissue renewal. Transcriptional profiling of Lgr6⁺and Lgr6⁻ cells did not reveal a distinct Lgr6-associated gene expression signature, raising the question of whether Lgr6 expression requires extrinsic niche signals. Our results elucidate the interrelation and behavior of Lgr6⁺ populations in the IFE, HF, and SG and suggest population asymmetry as a common mechanism for homeostasis in several epithelial skin compartments.We thank Åsa Bergström for technical help and assistance with mouse strains, Viljar Jaks for his help with FACS analysis, and Anna Johnsson and Peter Lönnerberg for conducting RNA-seq. This work was supported by grants from the Swedish Cancer Society, Swedish Research Council, H&G Jeanssons Foundation, Swedish Foundation for Strategic Research and Ragnar Söderberg Foundation (to M.K.), the Swedish Cancer Society, Swedish Research Council (to R.T.), the European Molecular Biology Organization (to A.H.), the Swedish Research Council (STARGET to M.K. and S.L.), and the Wellcome Trust (grant number 098357/Z/12/Z to B.D.S.). A.F. was supported by the EU FP7 ITN Healing Network. Parts of this study were performed at the (1) Live Cell Imaging unit, Department of Biosciences and Nutrition, Karolinska Institutet, Sweden, supported by grants from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Center for Innovative Medicine and the Jonasson donation to the School of Technology and Health, Royal Institute of Technology, Sweden, and (2) Wallenberg Institute for Regenerative Medicine Flow Cytometry Facility financed by Knut and Alice Wallenberg Foundation, Karolinska Institutet, Huddinge, Sweden.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.stemcr.2015.09.01