Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells

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Zhang, Bing ^{[1, 2]} ; Ma, Sai ^{[1, 3, 2, 4, 5]} ; Rachmin, Inbal ^[6] ; He, Megan ^{[7, 1, 2]} ; Baral, Pankaj ^[8] ; Choi, Sekyu ^{[1, 2]} ; Goncalves, William A. ^[9] ; Shwartz, Yulia ^{[1, 2]} ; Fast, Eva M. ^{[1, 10, 2, 11, 12]} ; Su, Yiqun ^[6] ; Zon, Leonard I. ^{[13, 1, 10, 2, 11, 12]} ; Regev, Aviv ^{[13, 3, 4, 5]} ; Buenrostro, Jason D. ^{[1, 2]} ; Cunha, Thiago M. ^{[8, 14]} ; Chiu, Isaac M. ^[8] ; Fisher, David E. ^[6] ; Hsu, Ya-Chieh ^{[1, 2]}

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^[1] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 - USA

^[2] Harvard Stem Cell Inst, Cambridge, MA 02138 - USA

^[3] MIT, Dept Biol, Cambridge, MA - USA

^[4] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 - USA

^[5] MIT, Koch Inst, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[6] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA - USA

^[7] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 - USA

^[8] Harvard Med Sch, Dept Immunol, Boston, MA 02115 - USA

^[9] Univ Fed Minas Gerais, Inst Biol Sci, Belo Horizonte, MG - Brazil

^[10] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 - USA

^[11] Boston Childrens Hosp, Stem Cell Program, Boston, MA - USA

^[12] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA - USA

^[13] Howard Hughes Med Inst, Chevy Chase, MD - USA

^[14] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, CRID, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Nature; JAN 2020.
• Citações Web of Science: 4

Resumo

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, chemogenetics(3,4), 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. Stress induces hair greying in mice through depletion of melanocyte stem cells, which is mediated by the activation of sympathetic nerves rather than through immune attack or adrenal stress hormones. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs