Journal article
Signalling by senescent melanocytes hyperactivates hair growth
Nature (London), Vol.618(7966), pp.808-817
06/22/2023
DOI: 10.1038/s41586-023-06172-8
PMID: 37344645
Abstract
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration
. 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 nevi
, 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 tissue
, 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.
Details
- Title: Subtitle
- Signalling by senescent melanocytes hyperactivates hair growth
- Creators
- Xiaojie Wang - University of California, IrvineRaul Ramos - University of California, IrvineAnne Q Phan - University of California, IrvineKosuke Yamaga - University of California, IrvineJessica L Flesher - University of California, IrvineShan Jiang - Yonsei UniversityJi Won Oh - Yonsei UniversitySuoqin Jin - University of California, IrvineSohail Jahid - National Taiwan UniversityChen-Hsiang Kuan - National Taiwan UniversityTruman Kt Nguyen - University of California, IrvineHeidi Y Liang - University of California, IrvineNitish Udupi Shettigar - University of California, IrvineRenzhi Hou - University of California, IrvineKevin H Tran - University of California, IrvineAndrew Nguyen - University of California, IrvineKimberly N Vu - University of California, IrvineJennie L Phung - University of California, IrvineJonard P Ingal - University of California, IrvineKatelyn M Levitt - University of California, IrvineXiaoling Cao - Central South UniversityYingzi Liu - Central South UniversityZhili Deng - Central South UniversityNobuhiko Taguchi - University of California, IrvineVanessa M Scarfone - University of California, IrvineGuangfang Wang - University of California, IrvineKara Nicole Paolilli - University of California, IrvineXiaoyang Wang - University of California, IrvineChristian F Guerrero-Juarez - University of California, IrvineRyan T Davis - University of California, IrvineElyse Noelani Greenberg - University of California, IrvineRolando Ruiz-Vega - University of California, IrvinePriya Vasudeva - University of California, IrvineRabi Murad - University of California, IrvineLily Halida Putri Widyastuti - University of BradfordHye-Lim Lee - University of California, IrvineKevin J McElwee - University of BradfordAlain-Pierre Gadeau - Biologie des maladies cardiovasculairesDevon A Lawson - University of California, IrvineBogi Andersen - University of California, IrvineAli Mortazavi - University of California, IrvineZhengquan Yu - Gifu UniversityQing Nie - University of California, IrvineTakahiro Kunisada - Universität UlmMichael Karin - University of California San DiegoJan Tuckermann - Universität UlmJeffrey D Esko - Central South UniversityAnand K Ganesan - University of California, IrvineJi Li - Central South UniversityMaksim V Plikus - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.618(7966), pp.808-817
- DOI
- 10.1038/s41586-023-06172-8
- PMID
- 37344645
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- U54 CA217378 / NCI NIH HHS U01 AR073159 / NIAMS NIH HHS R01 AR079470 / NIAMS NIH HHS R01 AR044882 / NIAMS NIH HHS T32 CA009054 / NCI NIH HHS R33 AR073031 / NIAMS NIH HHS R21 AR078939 / NIAMS NIH HHS R61 AR073031 / NIAMS NIH HHS T32 AR080622 / NIAMS NIH HHS R01 AR079150 / NIAMS NIH HHS
- Language
- English
- Date published
- 06/22/2023
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985214170702771
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