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. 2020 Jan;577(7792):676-681.
doi: 10.1038/s41586-020-1935-3. Epub 2020 Jan 22.

Hyperactivation of Sympathetic Nerves Drives Depletion of Melanocyte Stem Cells

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Free PMC article

Hyperactivation of Sympathetic Nerves Drives Depletion of Melanocyte Stem Cells

Bing Zhang et al. Nature. .
Free PMC article

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.

Conflict of interest statement

COMPETING INTERESTS

L.I.Z. is a founder and stockholder of Fate Therapeutics, Inc., Scholar Rock and Camp4 Therapeutics. D.E.F has a financial interest in Soltego, Inc., a company developing SIK inhibitors for topical skin darkening treatments that might be used for a broad set of human applications. D.E.F’s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. A.R. is an SAB member of ThermoFisher Scientific, Neogene Therapeutics, Asimov, and Syros Pharmaceuticals, an equity holder of Immunitas, and a founder and an equity holder of Celsius Therapeutics. I.M.C. is an SAB member of GSK pharmaceuticals and Kintai pharmaceuticals. A provisional patent application has been filed based on this work (Applicants: President and Fellows of Harvard College and The General Hospital Corporation; Inventors: Y-C.H., D.E.F., B.Z., and I.R.; Application number: 62/903,517; Status: pending/provisional; Aspect covered: Methods and compositions for controlling hair greying. All other authors declare no competing interests.

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