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Deciphering How Stress Influences Stem Cells and Tissue Regeneration

Review of “Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells” from Nature by Stuart P. Atkinson

While the greying of our hair has long since been linked to elevated levels of stress [1, 2], we currently have little insight into the mechanisms involved and the potential involvement of the hair follicle stem cells and melanocyte stem cells that support the production of pigmented hair [3, 4]. This situation led researchers from the laboratory of Ya-Chieh Hsu (Harvard University/Harvard Stem Cell Institute, Cambridge, MA, USA.) to investigate the melanocyte lineage to understand how stress influences tissue regeneration [5]. 

Excitingly, Zhang et al. now report that model mice undergoing acute stress suffer from the rapid loss of melanocyte stem cells and the appearance of har greying in a study that establishes how the overall physiological state of an organism can directly influence the maintenance of somatic stem cells and affect tissue regeneration.

The authors of this fascinating new study began by employing a battery of complementary techniques to highlight that immune attack or adrenal stress hormones (e.g., corticosterone) failed to influence the loss of melanocyte stem cells induced by nociception-induced stress achieved through an injection of a capsaicin analog. 

Instead, evidence suggested that the innervation of the melanocyte stem cell niche via the activation of sympathetic nerves leads to the burst release of the neurotransmitter noradrenaline (or norepinephrine), known to control our stress-related fight-or-flight responses, under conditions of stress. Neurotransmitter signaling then prompts the exit from quiescence and rapid proliferation of melanocyte stem cells, and subsequent differentiation, migration, and permanent deletion from the niche, which then culminates in damage to tissue regeneration, exemplified by hair graying.

As sympathetic nerves innervate essentially all organs, these findings suggest that acute stress may have a broad and rapid effect on many tissues; however, the team ended their study by demonstrating how the transient suppression of melanocyte stem cell proliferation during stress by the injection of cyclin-dependent kinase inhibitors prevented hair greying. Could this strategy represent a strategy to reduce stress-induced tissue regeneration deficits?

The authors note that further studies may aim to investigate how the above-described mechanism influences the loss of melanocyte stem cells associated with healthy aging and whether stress might mimic an accelerated aging process.

For more on the link between stem cells and the sympathetic nervous system, stay tuned to the Stem Cells Portal!


  1. Ephraim AJ, On Sudden or Rapid Whitening of the Hair. A.M.A. Archives of Dermatology 1959;79:228-236.
  2. A. Navarini A and Nobbe S, Marie Antoinette Syndrome. Archives of Dermatology 2009;145:656-656.
  3. Chang CY, Pasolli HA, Giannopoulou EG, et al., NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature 2013;495:98-102.
  4. Rabbani P, Takeo M, Chou W, et al., Coordinated activation of Wnt in epithelial and melanocyte stem cells initiates pigmented hair regeneration. Cell 2011;145:941-955.
  5. Zhang B, Ma S, Rachmin I, et al., Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature 2020;577:676-681.