eLife (Jul 2017)
A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning
- Qixuan Wang,
- Ji Won Oh,
- Hye-Lim Lee,
- Anukriti Dhar,
- Tao Peng,
- Raul Ramos,
- Christian Fernando Guerrero-Juarez,
- Xiaojie Wang,
- Ran Zhao,
- Xiaoling Cao,
- Jonathan Le,
- Melisa A Fuentes,
- Shelby C Jocoy,
- Antoni R Rossi,
- Brian Vu,
- Kim Pham,
- Xiaoyang Wang,
- Nanda Maya Mali,
- Jung Min Park,
- June-Hyug Choi,
- Hyunsu Lee,
- Julien M D Legrand,
- Eve Kandyba,
- Jung Chul Kim,
- Moonkyu Kim,
- John Foley,
- Zhengquan Yu,
- Krzysztof Kobielak,
- Bogi Andersen,
- Kiarash Khosrotehrani,
- Qing Nie,
- Maksim V Plikus
Affiliations
- Qixuan Wang
- ORCiD
- Department of Mathematics, University of California, Irvine, United States; Center for Complex Biological Systems, University of California, Irvine, United States
- Ji Won Oh
- ORCiD
- 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
- Hye-Lim Lee
- 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
- Anukriti Dhar
- 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
- Tao Peng
- Department of Mathematics, University of California, Irvine, United States
- Raul Ramos
- 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
- Christian Fernando Guerrero-Juarez
- 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
- Xiaojie Wang
- 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
- Ran Zhao
- 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; 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
- Xiaoling Cao
- 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 Burn Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Jonathan Le
- 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
- Melisa A Fuentes
- 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
- Shelby C Jocoy
- 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
- Antoni R Rossi
- 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
- Brian Vu
- 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
- Kim Pham
- 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
- Xiaoyang Wang
- 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
- Nanda Maya Mali
- Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea; Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea
- Jung Min Park
- Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea; Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea
- June-Hyug Choi
- Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea; Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea
- Hyunsu Lee
- Department of Anatomy, School of Medicine, Keimyung University, Daegu, Korea
- Julien M D Legrand
- UQ Diamantina Institute, Experimental Dermatology Group, Translational Research Institute, The University of Queensland, Brisbane, Australia
- Eve Kandyba
- ORCiD
- Department of Pathology, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, United States
- Jung Chul Kim
- Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
- Moonkyu Kim
- Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
- John Foley
- Department of Dermatology, Medical Sciences Program, Indiana University School of Medicine, Bloomington, United States
- Zhengquan Yu
- ORCiD
- 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
- Krzysztof Kobielak
- 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; Centre of New Technologies, CeNT, University of Warsaw, Warsaw, Poland
- Bogi Andersen
- ORCiD
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, United States; Departments of Medicine and Biological Chemistry, University of California, Irvine, United States
- Kiarash Khosrotehrani
- UQ Diamantina Institute, Experimental Dermatology Group, Translational Research Institute, The University of Queensland, Brisbane, Australia
- Qing Nie
- 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
- Maksim V Plikus
- ORCiD
- 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
- DOI
- https://doi.org/10.7554/eLife.22772
- Journal volume & issue
-
Vol. 6
Abstract
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.
Keywords
