Short heat shock has a long-term effect on mesenchymal stem cells' transcriptome

The adverse effects of heat stress (HS) on physiological systems are well docu-mented, yet the underlying molecular mechanisms behind it remain poorly under-stood. To address this knowledge gap, we conducted a comprehensive investiga-tion into the impact of HS on mesenchymal stem cells (MSCs), focusing on their morphology, phenotype, proliferative capacity, and fate determination. Our in-depth analysis of the MSCs' transcriptome revealed a significant influence of HS on the transcriptional landscape. Notably, even after a short period of stress, we observed a persistent alteration in cell identity, potentially mediated by the activation of bivalent genes. Furthermore, by comparing the differentially ex-pressed genes following short HS with their transcriptional state after recovery, we identified the transient upregulation of MLL and other histone modifiers, providing a potential mechanistic explanation for the stable activation of bivalent genes. This could be used to predict and modify the long-term effect of HS on cell identity.