洛克菲勒大学Elaine Fuchs研究小组取得一项新突破。他们发现了综合应激反应微调了丝氨酸剥夺和组织损伤后干细胞命运的决定。相关论文于2025年6月12日发表于国际顶尖学术期刊《细胞—代谢》杂志上。

小组发现丝氨酸是一种非常规的、非必需的氨基酸，它会影响这一过程。当膳食丝氨酸下降时，HFSCs中的内源性生物合成不能满足需求（反之亦然），减缓了毛发周期的进入。丝氨酸剥夺也会改变伤口修复，进一步延缓头发再生，同时加速再上皮化动力学。在机制上，课题组人员发现HFSCs通过触发综合应激反应来感知每个适应性挑战，这作为表皮-HF身份的变阻器。随着压力水平的上升，皮肤屏障恢复动力学加速，而头发生长被推迟。他们的发现为饮食和药物干预加速伤口愈合提供了可能。

据介绍，表皮干细胞产生皮肤的屏障，排除病原体，防止脱水。毛囊干细胞（HFSCs）致力于头发再生，但在受伤时，它们也可以重建并此后维持覆盖的表皮。HFSCs如何平衡这些命运选择以恢复受损组织的生理功能仍然知之甚少。

附：英文原文

Title: The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury

Author: Jesse S.S. Novak, Lisa Polak, Sanjeethan C. Baksh, Douglas W. Barrows, Marina Schernthanner, Benjamin T. Jackson, Elizabeth A.N. Thompson, Anita Gola, M. Deniz Abdusselamoglu, Alain R. Bonny, Kevin A.U. Gonzales, Julia S. Brunner, Anna E. Bridgeman, Katie S. 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

Issue&Volume: 2025-06-12

Abstract: 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.

DOI: 10.1016/j.cmet.2025.05.010

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00266-9