title: Organ-level quorum sensing directs regeneration in hair stem cell populations.
abstract: Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair plucking, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Plucking hair at different densities leads to a regeneration of up to five times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α-secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells.
authors: Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA; Department of Dermatology, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC; Institute of Clinical Medicine and Department of Dermatology, National Yang-Ming University, Taipei, Taiwan 112, ROC.
authors: Chih-Chiang
authors: CC
authors: Chen
authors: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Lei
authors: L
authors: Wang
authors: Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California Irvine, Irvine, CA 92697, USA.
authors: Maksim V
authors: MV
authors: Plikus
authors: Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA.
authors: Ting Xin
authors: TX
authors: Jiang
authors: Division of Mathematics, University of Dundee, Dundee DD1 4HN, UK.
authors: Philip J
authors: PJ
authors: Murray
authors: Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California Irvine, Irvine, CA 92697, USA.
authors: Raul
authors: R
authors: Ramos
authors: Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California Irvine, Irvine, CA 92697, USA.
authors: Christian F
authors: CF
authors: Guerrero-Juarez
authors: International Laboratory of Wound Repair and Regeneration and Institute of Clinical Medicine, National Cheng Kung University, Tainan 701, Taiwan, ROC.
authors: Michael W
authors: MW
authors: Hughes
authors: Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei and Center for Stem Cell Research, National Yang-Ming University and Veterans General Hospital, Taipei 112, Taiwan, ROC.
authors: Oscar K
authors: OK
authors: Lee
authors: Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA.
authors: Songtao
authors: S
authors: Shi
authors: Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA.
authors: Randall B
authors: RB
authors: Widelitz
authors: Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California Irvine, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA.
authors: Arthur D
authors: AD
authors: Lander
authors: Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA; Institute of Clinical Medicine and Department of Dermatology, National Yang-Ming University, Taipei, Taiwan 112, ROC; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 10617, Taiwan. Electronic address: cmchuong@usc.edu.
authors: Cheng Ming
authors: CM
authors: Chuong
mesh_terms: D000818:Animals; D002450:Cell Communication; D018932:Chemokine CCL2 / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha