The Integrated Stress Response Fine-Tunes Stem Cell Fate Decisions Upon Serine Deprivation and Tissue Injury

June 2025 in “ Cell Metabolism ”

Jesse Novak, Lisa Polak, Sanjeethan C. Baksh, Douglas Barrows, Marina Schernthanner, Benjamin T. Jackson, Erik W. Thompson, Anita Gola, Merve Deniz Abdusselamoglu, Alain R. Bonny, Kevin Andrew Uy Gonzales, Julia Brunner, Anna E Bridgeman, K Stewart, Lynette Hidalgo, June dela Cruz-Racelis, Ji‐Dung Luo, Shiri Gur‐Cohen, H. Amalia Pasolli, Thomas S. Carroll, Lydia W.S. Finley, Elaine Fuchs

hair follicle stem cells serine integrated stress response epidermal repair hair regeneration wound healing

TLDR Serine is vital for hair follicle stem cells to balance hair growth and skin repair.

The study explores the role of serine in hair follicle stem cells (HFSCs) during serine deprivation and tissue injury, revealing that serine deficiency activates the integrated stress response (ISR), which shifts HFSCs towards an epidermal stem cell identity, enhancing wound healing but delaying hair regeneration. Experiments on C57BL/6J mice showed that a serine-deficient diet delayed hair regrowth but accelerated re-epithelialization. The study suggests that dietary and pharmacological interventions targeting serine levels could improve wound healing and treat conditions like alopecia. The findings underscore the importance of serine metabolism in skin stem cell function and its potential therapeutic implications.

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