Lyu Xiaolin, Xu Wenan, Zhou Jian, Chen Xiaohang, Yi Wenjing, Chen Leyi, Wang Ziting, Wang Songlin, Wu Buling
Shenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, Guangdong, China; Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University, Shenzhen, Guangdong, China.
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China; Department of VIP Dental Service, School of Stomatology, Capital Medical University, Beijing, China; Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Tissue Cell. 2025 Apr;93:102758. doi: 10.1016/j.tice.2025.102758. Epub 2025 Jan 26.
Cellular senescence prevents the application of mesenchymal stem cells in tissue engineering and stem cell therapy. Effective regulation of senescence is the key to maintain the functional stability of mesenchymal stem cells and improve their clinical application. This study aims to explore the molecular mechanism changes in human dental pulp stem cells (hDPSCs) during replicative senescence, focusing on the potential role of pregnancy-specific glycoprotein (PSGs) family member PSG4 in modulating cellular senescence. RNA sequencing was performed on hDPSCs at different passages and with PSG4 overexpression to reveal changes in gene expression during the process. Gain- and loss-of-function studies suggested that PSG4 regulated cellular senescence. PSG4 expression levels were significantly elevated during cellular senescence and closely correlated with cell cycle regulation. This study provides new insights into the molecular mechanisms underlying of hDPSCs' replicative senescence. PSG4 acts as a pivotal regulator of replicative senescence in hDPSCs by impacting cell cycle process.
细胞衰老阻碍了间充质干细胞在组织工程和干细胞治疗中的应用。有效调控衰老过程是维持间充质干细胞功能稳定性并改善其临床应用的关键。本研究旨在探索人牙髓干细胞（hDPSCs）在复制性衰老过程中的分子机制变化，重点关注妊娠特异性糖蛋白（PSGs）家族成员PSG4在调节细胞衰老中的潜在作用。对不同传代及过表达PSG4的hDPSCs进行RNA测序，以揭示该过程中基因表达的变化。功能获得和缺失研究表明，PSG4可调节细胞衰老。在细胞衰老过程中，PSG4表达水平显著升高，且与细胞周期调控密切相关。本研究为hDPSCs复制性衰老的分子机制提供了新见解。PSG4通过影响细胞周期进程，成为hDPSCs复制性衰老的关键调节因子。
