Rockefeller University scientists report that, in mice, hair follicle stem cells switch from fueling hair growth to repairing wounds when the amino acid serine is scarce — a shift governed by the integrated stress response. The peer‑reviewed findings in Cell Metabolism suggest dietary or drug strategies could eventually help speed wound healing.
Researchers have long held that adult skin relies on two main stem‑cell pools: epidermal stem cells to maintain the barrier and hair follicle stem cells (HFSCs) to regenerate hair. The new work shows HFSCs can pivot under stress, rerouting effort from hair growth to wound repair when serine levels drop — a cue that activates the integrated stress response (ISR). Serine is a non‑essential amino acid found in foods such as meat, grains, and milk. (sciencedaily.com)
The study, “The integrated stress response fine‑tunes stem cell fate decisions upon serine deprivation and tissue injury,” was published online June 12, 2025, and appears in the August 5, 2025 print issue of Cell Metabolism (37:8, pp. 1715–1731.e11; DOI: 10.1016/j.cmet.2025.05.010). (pubmed.ncbi.nlm.nih.gov)
Working in mice, the team either removed serine from the diet or blocked HFSCs’ ability to synthesize it. Low serine slowed entry into the hair cycle; when combined with skin injury, ISR activity rose further, suppressing hair growth and prioritizing re‑epithelialization. “Serine deprivation triggers a highly sensitive cellular ‘dial’ that fine tunes the cell’s fate — towards skin and away from hair,” said first author Jesse Novak, an MD‑PhD student in Weill Cornell’s Tri‑Institutional MD‑PhD Program and former Ph.D. student in Elaine Fuchs’s lab. (pubmed.ncbi.nlm.nih.gov)
“Most skin wounds that we get are from abrasions, which destroy the upper part of the skin,” Novak said. “That area is home to a pool of stem cells that normally takes charge in wound repair. But when these cells are destroyed, it forces hair follicle stem cells to take the lead.” (rockefeller.edu)
The authors note that earlier work from the Fuchs lab linked dietary serine restriction to curbing precancerous skin cells, prompting trials that explore serine‑limited diets in oncology. The current study examines how serine scarcity reshapes regeneration in healthy tissues. (rockefeller.edu)
Despite that influence, the body tightly regulates circulating serine: feeding mice six times the usual dietary serine raised levels by only about 50%. Even so, in HFSCs unable to make their own serine, a high‑serine diet partially restored hair regeneration. (sciencedaily.com)
“No one likes to lose hair, but when it comes down to survival in stressful times, repairing the epidermis takes precedence,” Fuchs said, adding that the group will test whether lowering serine intake or using ISR‑targeting drugs can accelerate wound closure, and whether other amino acids have similar effects. (sciencedaily.com)
