title: Self-organizing and stochastic behaviors during the regeneration of hair stem cells.
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.
authors.affiliation: Department of Pathology, University of Southern California (USC), Los Angeles, CA 90033, USA.
authors.forename: Maksim V
authors.initials: MV
authors.lastname: Plikus
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Baker
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chen
authors.forename: Clyde
authors.initials: C
authors.lastname: Fare
authors.forename: Damon
authors.initials: D
authors.lastname: de la Cruz
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.forename: Philip K
authors.initials: PK
authors.lastname: Maini
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Millar
authors.forename: Randall
authors.initials: R
authors.lastname: Widelitz
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Chuong
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D003198:Computer Simulation; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011817:Rabbits; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*; D013269:Stochastic Processes; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D051153:Wnt Proteins