Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells
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Bing_Nature_stress_skin.pdf
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Submitted version
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14.39 MB
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Author(s) • • • • • • • • •
Zhang, Bing
Ma, Sai
Rachmin, Inbal
He, Megan
Baral, Pankaj
Choi, Sekyu
Gonçalves, William A.
Shwartz, Yulia
Fast, Eva M.
Su, Yiqun
Alternative Title
Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells
Date Issued
January 2020
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Zhang, Bing et al. "Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells." Nature 577, 7792 (January 2020): 676–681 © 2020 The Author(s)
Version
Original manuscript
Abstract
Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)1,2, but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics3,4, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.
Subjects
Multidisciplinary
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41586-020-1935-3