CHARACTERIZATION OF THE HEAT SHOCK RESPONSE IN HUMAN CELL LINES USING TRANSCRIPTOMICS

Cellular stress response (CSR) is a highly conserved system that mitigates threats to cellular survival. The heat shock response is a part of the CSR that uses molecular chaperones to respond to temperature increases. Though the HSR is well-studied in various organisms, there is a lack of comparative analyses of multiple cell lines. We hypothesize that cancer cells will exhibit additional, unique modifications to their stress response along with the canonical heat shock response being activated in multiple cell types. Here, we subjected HEK293, HepG2, and HeLa cells to control heat shock or heat shock with eight hours of recovery at the control temperature. RNA sequencing was used to determine a transcriptome for each condition. The resulting transcriptome demonstrated unique responses to heat shock in all three cell lines, specifically increased activity in HepG2. Functional enrichment analysis showed the activation of canonical heat shock response pathways, including the unfolded protein response, as well as non-canonical heat shock response pathways. The non-canonical pathway “Receptor Ligand Activity” was enriched in all three cell lines. Molecular validation of this pathway via qPCR verified the activation of key “Receptor Ligand Activity” genes 0 hours and 8 hours post-heat shock. With these insights, we provide information to build a comprehensive model of the HSR in mammals while providing a foundation for future studies into cancer therapies targeting the HSR.