Self-organizing and stochastic behaviors during the regeneration of hair stem cells |
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Authors: | Plikus Maksim V Baker Ruth E Chen Chih-Chiang Fare Clyde de la Cruz Damon Andl Thomas Maini Philip K Millar Sarah E Widelitz Randall Chuong Cheng-Ming |
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Affiliation: | Department of Pathology, University of Southern California (USC), Los Angeles, CA 90033, USA. |
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Abstract: | Stem cells cycle through active and quiescent states. Large populations of stem cells in an organ may cycle randomly or in a coordinated manner. Although stem cell cycling within single hair follicles has been studied, less is known about regenerative behavior in a hair follicle population. By combining predictive mathematical modeling with in vivo studies in mice and rabbits, we show that a follicle progresses through cycling stages by continuous integration of inputs from intrinsic follicular and extrinsic environmental signals based on universal patterning principles. Signaling from the WNT/bone morphogenetic protein activator/inhibitor pair is coopted to mediate interactions among follicles in the population. This regenerative strategy is robust and versatile because relative activator/inhibitor strengths can be modulated easily, adapting the organism to different physiological and evolutionary needs. |
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