Diverse and Specific Gene Expression Responses to Stresses in Cultured Human Cells

TLDR

We used cDNA microarrays to systematically examine gene expression responses of HeLa cells and primary human lung fibroblasts to heat shock, endoplasmic reticulum stress, oxidative stress, and crowding. Clustering revealed stress‑specific and multi‑stress gene groups, with fewer genes up‑regulated by multiple stresses than in yeast, and showed that multi‑stress genes mainly involve cell‑cell communication; it also uncovered distinct stress‑responsive patterns between HeLa cells and fibroblasts, such as oxidative‑stress‑induced genes in fibroblasts but not HeLa, and heat‑shock‑induced transcription factors in HeLa but not fibroblasts. The dataset is freely available for search and download at http://microarray-pubs.stanford.edu/human_stress/Home.shtml.

Abstract

We used cDNA microarrays in a systematic study of the gene expression responses of HeLa cells and primary human lung fibroblasts to heat shock, endoplasmic reticulum stress, oxidative stress, and crowding. Hierarchical clustering of the data revealed groups of genes with coherent biological themes, including genes that responded to specific stresses and others that responded to multiple types of stress. Fewer genes increased in expression after multiple stresses than in free-living yeasts, which have a large general stress response program. Most of the genes induced by multiple diverse stresses are involved in cell-cell communication and other processes specific to higher organisms. We found substantial differences between the stress responses of HeLa cells and primary fibroblasts. For example, many genes were induced by oxidative stress and dithiothreitol in fibroblasts but not HeLa cells; conversely, a group of transcription factors, including c-fos and c-jun, were induced by heat shock in HeLa cells but not in fibroblasts. The dataset is freely available for search and download at http://microarray-pubs.stanford.edu/human_stress/Home.shtml.