Short heat stress has a long-term effect on mesenchymal stem cells transctiptome

Heat stress (HS) can seriously impact the health of both humans and animals. At the cellular level, HS elevates oxidative stress, decreases proliferation rate, and induces an earlier onset of cellular aging. However, little is known about the effects of HS on cells transcriptome landscape. Here we use an in vitro experimental system to address how heat shock treatment influences the transcriptome of bovine mesenchymal stem cells (MSCs), the multipotent progenitor cells that are found in most tissues and can differentiate into many cell types, regulate immune responses and maintain physiological homeostasis. To this end, the bovine MSCs were exposed to mild HS for different durations, and RNA sequencing and bioinformatic analysis were performed. Bioinformatics analysis indicate that heat stress influences many cell processes, namely immune response, differentiation, cell cycle and cellular stress response, as well as alteres expression of chromatin modifiers, especially KMTases. Interestingly, once normothermia resumes, the transcriptional pattern tends to revert to the typical MSC transcriptome, with only minimal number of genes differentially expressed. However, the phenotype of the cells is altered, with longer population doubling time and higher sensitivity to heat shock. In addition, there is a long-term effect of short heat stress on MSCs fate, possibly regulated by the activation of bivalent genes. Our preliminary results regariding MSCs differentiation to adipocytes and chondrocytes, following HS, support long-term effect of short HS on MSCs fate. We hypothesize that the epigenetic changes induced by heat shock convey a long lasting phenotypical change in the cells.