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Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells
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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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8 _, q3 M3 \* n/ N6 r- oStem cells cycle through active and quiescent states. Large populations of stem cells in an organ may cycle randomly or ina 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 andextrinsic environmental signals based on universal patterning principles. Signaling from the WNT/bone morphogenetic proteinactivator/inhibitor pair is coopted to mediate interactions among follicles in the population. This regenerative strategyis robust and versatile because relative activator/inhibitor strengths can be modulated easily, adapting the organism to differentphysiological and evolutionary needs. |
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