Resumen de Decoding the nature of the transcriptional response to stress
Virtually all living organisms are challenged by changes in their environment, such as sudden increases in osmolarity. To cope with these stresses, cells have developed stress responses that tune every aspect of cell physiology. Upon osmostress, Saccharomyces cerevisiae (yeast) cells undertake a massive reprogramming of gene expression essential for stress adaptation. This thesis aimed to provide a deeper understanding of these massive transcriptome changes caused by osmostress. To this end, we generated a highly-replicated bulk RNA-seq catalog of yeast osmostress-responsive genes that we comprehensively characterized in terms of gene features. We extended this analysis to human HeLa cells and observed conservation despite long evolutionary distances. To expose the differences between bulk and single-cell yeast transcriptomes in response to osmostress, we developed yeast single-cell RNA-seq (yscRNA-seq), a robust scRNA-seq method that overcomes yeast’s difficulties for single-cell. The application of yscRNA-seq to study cell-to-cell variability upon osmostress revealed a high degree of heterogeneity and gene-specific dynamic changes in gene expression variability. In summary, this thesis provides a holistic understanding of the nature of the transcriptional stress response.
