Molecular changes of cellular senescence in dental pulp stem cells during in vitro culture: A potential role of PSG4

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.