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Science 332 (6029): 586-589

Copyright © 2011 by the American Association for the Advancement of Science

Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells

Maksim V. Plikus,1 Ruth E. Baker,2 Chih-Chiang Chen,1,3 Clyde Fare,4 Damon de la Cruz,1 Thomas Andl,5 Philip K. Maini,2,6 Sarah E. Millar,7 Randall Widelitz,1 Cheng-Ming Chuong1,8,*

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.

1 Department of Pathology, University of Southern California (USC), Los Angeles, CA 90033, USA.
2 Centre for Mathematical Biology, Mathematical Institute, 24-29 St. Giles’, Oxford OX1 3LB, UK.
3 Institute of Clinical Medicine and Department of Dermatology, National Yang-Ming University and Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.
4 Life Sciences Interface Doctoral Training Centre, Wolfson Building, Parks Road, Oxford OX1 3QD, UK.
5 Vanderbilt University Medical Center, Nashville, TN 37232, USA.
6 Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.
7 Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA.
8 Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taiwan.

* To whom correspondence should be addressed. E-mail: cmchuong{at}usc.edu

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