title: Hair follicle stem cell cultures reveal self-organizing plasticity of stem cells and their progeny.
abstract: Understanding how complex tissues are formed, maintained, and regenerated through local growth, differentiation, and remodeling requires knowledge on how single-cell behaviors are coordinated on the population level. The self-renewing hair follicle, maintained by a distinct stem cell population, represents an excellent paradigm to address this question. A major obstacle in mechanistic understanding of hair follicle stem cell (HFSC) regulation has been the lack of a culture system that recapitulates HFSC behavior while allowing their precise monitoring and manipulation. Here, we establish an in vitro culture system based on a 3D extracellular matrix environment and defined soluble factors, which for the first time allows expansion and long-term maintenance of murine multipotent HFSCs in the absence of heterologous cell types. Strikingly, this scheme promotes de novo generation of HFSCs from non-HFSCs and vice versa in a dynamic self-organizing process. This bidirectional interconversion of HFSCs and their progeny drives the system into a population equilibrium state. Our study uncovers regulatory dynamics by which phenotypic plasticity of cells drives population-level homeostasis within a niche, and provides a discovery tool for studies on adult stem cell fate.
authors.affiliation: Paul Gerson Unna Group "Skin Homeostasis and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Carlos Andrés
authors.initials: CA
authors.lastname: Chacón-Martínez
authors.affiliation: Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Klose
authors.affiliation: Institute for Biochemistry II, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Catherin
authors.initials: C
authors.lastname: Niemann
authors.affiliation: Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Glauche
authors.affiliation: Paul Gerson Unna Group "Skin Homeostasis and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany wickstroem@age.mpg.de.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Sara A
authors.identifier: 0000-0001-6383-6292
authors.initials: SA
authors.lastname: Wickström
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D018859:Hair Follicle / Q000166:cytology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*
keywords: differentiation; hair follicle stem cells; niche; reprogramming; stem cell cultures