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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Signalling by senescent melanocytes hyperactivates hair growth
Xiaojie Wang1,2,3, Raul Ramos4,5,6, Anne Q Phan7
1Department of Developmental and Cell Biology, University of California, Irvine, CA, USA. xiaojiw2@uci.edu.
Nature
|June 21, 2023
Summary
Senescent nevus melanocytes secrete osteopontin, driving hair stem cells to regenerate hair. This discovery highlights senescent cells as potential therapeutic targets for regenerative disorders.
Area of Science:
- Cell Biology
- Dermatology
- Regenerative Medicine
Background:
- Niche signals regulate stem cell quiescence and activation for tissue regeneration.
- Dysregulated niche signaling contributes to regenerative disorders.
- Melanocytic nevi are associated with excessive hair growth, indicating hair stem cell hyperactivity.
Purpose of the Study:
- To investigate the role of senescent melanocytes in nevus-associated hair growth.
- To identify the molecular mechanisms by which nevus melanocytes influence hair stem cells.
- To explore the therapeutic potential of targeting senescent cell signaling in regenerative disorders.
Main Methods:
- Utilized genetic mouse models of nevi.
- Analyzed the secretome of nevus melanocytes.
- Investigated the role of osteopontin and its receptor CD44.
- Examined human hairy nevi samples.
Main Results:
- Senescent melanocytes in nevi induce hair stem cells to exit quiescence and enhance hair renewal.
- Osteopontin is a key signaling factor secreted by nevus melanocytes, promoting hair growth.
- Osteopontin and CD44 genetic deletion rescued enhanced hair growth.
- Osteopontin is overexpressed in human hairy nevi and stimulates human hair follicle growth.
Conclusions:
- Signaling from senescent cell clusters can enhance adjacent stem cell activity and stimulate tissue renewal.
- Senescent melanocytes and their secretome, particularly osteopontin, are potent drivers of hair regeneration.
- Senescent cells represent a promising therapeutic target for regenerative medicine.
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