Dr. Sharon Schlesinger

Heat stress (HS) can have a serious impact on 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. Because cattle are sensitive to harsh external temperatures, studying the effects of HS on MSCs provides a unique platform to address cellular stress in a physiologically relevant model organism. To this end, MSCs were extracted from the umbilical cord of a bovine fetus and cultured in the lab. After validation of the cells as MSCs, the cells were exposed to mild HS for different durations. At the end of the experiment, RNA sequencing and bioinformatic analysis were performed. Bioinformatics analysis indicates that heat stress influences many cell processes, namely immune response, differentiation, cell cycle, and cellular stress response, as well as altered the expression of chromatin modifiers, especially KMTases. Interestingly, once normothermia resumes, the transcriptional pattern tends to revert to the typical MSC transcriptome, with only a minimal number of genes differentially expressed. However, the phenotype of the cells is altered, with a longer population doubling time and higher sensitivity to heat shock. We hypothesize that the epigenetic changes induced by heat shock convey a long-lasting phenotypical change in the cells.