近日，美国斯坦福医学院教授Helen M. Blau及其小组探明了多组学分析显示，前列腺素E2逆转衰老肌肉干细胞功能障碍，导致再生和力量增加。相关论文于2025年6月12日发表于国际顶尖学术期刊《细胞—干细胞》杂志上。

该课题组研究人员发现衰老的MuSCs已经减弱了前列腺素E2 (PGE2)-EP4受体信号，这导致了它们的早裂和有丝分裂灾难。使用PGE2治疗可改变染色质可及性，克服功能失调的老年MuSC命运轨迹，增加活力并触发细胞周期重新进入。该团队使用神经网络模型来学习驱动可及性变化的转录因子的复杂逻辑。在PGE2处理后，课题组检测到CRE和E-box基序位点的转录因子结合增加，AP1基序位点的结合减少，克服了随年龄变化而发生的变化。该团队发现衰老的MuSCs短期暴露于PGE2增强了它们移植后的长期再生能力。引人注目的是，在肌毒素或运动诱导的损伤后注射PGE2克服了老化的生态位，导致内源性组织常驻MuSCs的再生功能增强和强度增加。

据介绍，由于功能失调的骨髓干细胞（MuSCs）的积累，细胞损伤的修复能力随着年龄的增长而下降。

附：英文原文

Title: Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength

Author: Yu Xin Wang, Adelaida R. Palla, Andrew T.V. Ho, Daniel C.L. Robinson, Meenakshi Ravichandran, Glenn J. Markov, Thach Mai, Chris Still, Akshay Balsubramani, Surag Nair, Colin A. Holbrook, Ann V. Yang, Peggy E. Kraft, Shiqi Su, David M. Burns, Nora D. Yucel, Lei S. Qi, Anshul Kundaje, Helen M. Blau

Issue&Volume: 2025-06-12

Abstract: Repair of muscle damage declines with age due to the accumulation of dysfunctional muscle stem cells (MuSCs). Here, we uncover that aged MuSCs have blunted prostaglandin E2 (PGE2)-EP4 receptor signaling, which causes precocious commitment and mitotic catastrophe. Treatment with PGE2 alters chromatin accessibility and overcomes the dysfunctional aged MuSC fate trajectory, increasing viability and triggering cell cycle re-entry. We employ neural network models to learn the complex logic of transcription factors driving the change in accessibility. After PGE2 treatment, we detect increased transcription factor binding at sites with CRE and E-box motifs and reduced binding at sites with AP1 motifs, overcoming the changes that occur with age. We find that short-term exposure of aged MuSCs to PGE2 augments their long-term regenerative capacity upon transplantation. Strikingly, PGE2 injections following myotoxin- or exercise-induced injury overcome the aged niche, leading to enhanced regenerative function of endogenous tissue-resident MuSCs and an increase in strength.

DOI: 10.1016/j.stem.2025.05.012

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00192-4