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Elife. 2017 Jul 11;6. pii: e22772. doi: 10.7554/eLife.22772.

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning.

Wang Q#1,2, Oh JW#3,4,5,6,7, Lee HL3,4, Dhar A3,4, Peng T1, Ramos R3,4, Guerrero-Juarez CF3,4, Wang X3,4, Zhao R3,4,8, Cao X3,4,9, Le J3,4, Fuentes MA3,4, Jocoy SC3,4, Rossi AR3,4, Vu B3,4, Pham K3,4, Wang X3,4, Mali NM5,6, Park JM5,6, Choi JH5,6, Lee H10, Legrand JMD11, Kandyba E12, Kim JC7, Kim M7, Foley J13, Yu Z8, Kobielak K3,4,14, Andersen B4,15, Khosrotehrani K11, Nie Q1,2,3, Plikus MV2,3,4.

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Department of Mathematics, University of California, Irvine, United States.
Center for Complex Biological Systems, University of California, Irvine, United States.
Department of Developmental and Cell Biology, University of California, Irvine, United States.
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, United States.
Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea.
Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea.
Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea.
Beijing Advanced Innovation Center for Food Nutrition and Human Health and State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
Department of Burn Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Anatomy, School of Medicine, Keimyung University, Daegu, Korea.
UQ Diamantina Institute, Experimental Dermatology Group, Translational Research Institute, The University of Queensland, Brisbane, Australia.
Department of Pathology, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, United States.
Department of Dermatology, Medical Sciences Program, Indiana University School of Medicine, Bloomington, United States.
Centre of New Technologies, CeNT, University of Warsaw, Warsaw, Poland.
Departments of Medicine and Biological Chemistry, University of California, Irvine, United States.
Contributed equally


The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.


computational biology; developmental biology; hair follicle; mouse; pattern formation; skin; stem cells; systems biology

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