TY - JOUR
T1 - Organ-level quorum sensing directs regeneration in hair stem cell populations
AU - Chen, Chih Chiang
AU - Wang, Lei
AU - Plikus, Maksim V.
AU - Jiang, Ting Xin
AU - Murray, Philip J.
AU - Ramos, Raul
AU - Guerrero-Juarez, Christian F.
AU - Hughes, Michael W.
AU - Lee, Oscar K.
AU - Shi, Songtao
AU - Widelitz, Randall B.
AU - Lander, Arthur D.
AU - Chuong, Cheng Ming
N1 - Funding Information:
C.M.C., T.X.J., and R.B.W. are supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) RO1-AR42177, AR 47364, and AR60306. C.C.C. is supported by NSC 100-2314-B-075-044, NSC 101-2314-B-075-008-MY3, and the Taipei Veterans General Hospital (VN103-12, V103C-010, V102B-009, R-1100403). A.D.L. is supported by NIGMS P50-GM076516. S.S. is supported by NIH R01DE17449. L.W. is supported by the National Natural Science Foundation of China (81270015). M.V.P. is supported by NIAMS R01-AR067273 and Edward Mallinckrodt Jr. Foundation grant. R.R. is supported by a California Institute of Regenerative Medicine (CIRM) training grant (TG2-01152). C.F.G.-J. is supported by the National Science Foundation Graduate Research Fellowship Program (DGE-1321846). P.J.M. is supported by a post-doctoral and early career researcher exchange fellowship from the Northern Research Parternship (NRP). M.W.H. is supported by Top Notch University plan of CKU, Taiwan. We thank Drs. Jaw-Ching Wu, Han-Nan Liu, and Yun-Ting Chang of National Yang Ming University/Taipei Veterans General hospital for their support. Invention number 2014-255 “Enhance hair growth via plucking” (D2014-0054) was disclosed to University of Southern California.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/9
Y1 - 2015/4/9
N2 - Summary 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.
AB - Summary 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.
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U2 - 10.1016/j.cell.2015.02.016
DO - 10.1016/j.cell.2015.02.016
M3 - Article
C2 - 25860610
AN - SCOPUS:84927169525
VL - 161
SP - 277
EP - 290
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -