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Novak, J. S. S., Polak, L., & Baksh, S. C. (2025). The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury. Cell Metabolism. 
Added by: Dr. Enrique Feoli (20/07/2025, 17:31)   Last edited by: Dr. Enrique Feoli (20/07/2025, 17:38)
Resource type: Journal Article
ID no. (ISBN etc.): 1550-4131
BibTeX citation key: Novak2025
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 Categories: BioAcyl Corp
Subcategories: Stress response
Creators: Baksh, Novak, Polak
Publisher: Cell Press
Collection: Cell Metabolism		 Views: 3/19
Abstract

Highlights

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Deprivation of the non-essential amino acid serine activates the integrated stress response (ISR) in vivo
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The ISR favors epidermal fate and represses hair follicle fate
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Upon injury, serine-deprived HFSCs repair wounds faster and delay hair regeneration
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Pharmacologic and metabolic interventions can be used to improve wound healing

Summary

Epidermal stem cells produce the skin’s barrier that excludes pathogens and prevents dehydration. Hair follicle stem cells (HFSCs) are dedicated to bursts of hair regeneration, but upon injury, they can also reconstruct, and thereafter maintain, the overlying epidermis. How HFSCs balance these fate choices to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover serine as an unconventional, non-essential amino acid that impacts this process. When dietary serine dips, endogenous biosynthesis in HFSCs fails to meet demands (and vice versa), slowing hair cycle entry. Serine deprivation also alters wound repair, further delaying hair regeneration while accelerating re-epithelialization kinetics. Mechanistically, we show that HFSCs sense each fitness challenge by triggering the integrated stress response, which acts as a rheostat of epidermal-HF identity. As stress levels rise, skin barrier restoration kinetics accelerate while hair growth is delayed. Our findings offer potential for dietary and pharmacological intervention to accelerate wound healing

  
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