Signalling by senescent melanocytes hyperactivates hair growth

Nature. 2023; 618(7966): 808–817.
Published online 2023 Jun 21. doi: 10.1038/s41586-023-06172-8

Signalling by senescent melanocytes hyperactivates hair growth

Xiaojie Wang,corresponding author1,2,3 Raul Ramos,1,2,3 Anne Q. Phan,4 Kosuke Yamaga,1,2 Jessica L. Flesher,5 Shan Jiang,1,6 Ji Won Oh,7,8 Suoqin Jin,9,10 Sohail Jahid,5 Chen-Hsiang Kuan,1,2,11,12 Truman Kt Nguyen,1,2 Heidi Y. Liang,1,2 Nitish Udupi Shettigar,1,2,13 Renzhi Hou,1,2,3 Kevin H. Tran,1,2 Andrew Nguyen,1,2 Kimberly N. Vu,1,2 Jennie L. Phung,1,2 Jonard P. Ingal,1,2 Katelyn M. Levitt,1,2 Xiaoling Cao,1,2 Yingzi Liu,1,2,14 Zhili Deng,14 Nobuhiko Taguchi,15 Vanessa M. Scarfone,2 Guangfang Wang,2 Kara Nicole Paolilli,2 Xiaoyang Wang,2 Christian F. Guerrero-Juarez,1,2,3,6,9 Ryan T. Davis,16 Elyse Noelani Greenberg,5 Rolando Ruiz-Vega,5 Priya Vasudeva,5 Rabi Murad,1,6 Lily Halida Putri Widyastuti,2 Hye-Lim Lee,1,2 Kevin J. McElwee,17 Alain-Pierre Gadeau,18 Devon A. Lawson,16 Bogi Andersen,2,3,5,19 Ali Mortazavi,1,6 Zhengquan Yu,20 Qing Nie,1,3,6,9 Takahiro Kunisada,15 Michael Karin,21 Jan Tuckermann,22,23 Jeffrey D. Esko,4 Anand K. Ganesan,5,24 Ji Li,14,25 and Maksim V. Plikuscorresponding author1,2,3,6,13

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Subject terms: Senescence, Skin stem cells, Stem-cell niche, Extracellular signalling molecules

Note:

Conflict of interest statement

M.V.P. is an inventor on a patent application filed by the University of California, Irvine describing the use of senescent secretome factors for promoting hair growth, among other claims. M.V.P. is also a co-founder and Chief Scientific Officer at the Amplifica Holdings Group, Inc. N.U.S. is employed by the Amplifica Holdings Group, Inc. All other authors declare no competing interests.

Long form: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284692/

Osteopontin sounds a little scary since it is involved in tumor growth. I wonder how it can be applied locally for hair growth without it moving around and possibly helping cancers grow.

shaftless wrote:Osteopontin sounds a little scary since it is involved in tumor growth. I wonder how it can be applied locally for hair growth without it moving around and possibly helping cancers grow.

Osteopontin can be enhanced by some natural stuff we might be already taking, such as Turmeric (Curcumin),
Vitamin D foods, etc.