Transcriptomic landscape of human primary stromal cells upon chemotherapeutic and/or PDK4-specific intervention

Cellular senescence is a response elicited by acute or chronic damage signals. In humans, senescent cells accumulate in multiple tissues at different rates, from 2- to 20-fold when comparing young (<35 years) to old (>65 years) healthy donors. The pathogenic role of cellular senescence in diverse age-related diseases can be largely explained by the senescence-associated secretory phenotype (SASP). Senescent cells display changes in mitochondrial activity with increased ATP production and high lactate production, which are partially correlated with upregulation of pyruvate dehydrogenase kinase 4 (PDK4), an inhibitor of mitochondrial pyruvate dehydrogenase. We used a genotoxic agent, bleomycin, and/or a PDK4-targeting chemical, PDK4-IN, to treat human primary stromal cells and determined the influence of PDK4 inhibition on the transcriptomic expression profile of senescent cells. The data allow to disclose the importance of PDK4 activity in development of senescence-associated phenotypes, particularly the SASP. Overall design: High-throughput RNA-seq examination of genome-wide transcriptional alterations of human primary stromal cells that underwent treatment by the chemotherapeutic agent bleomycin and/or a PDK4-specific inhibitor PDK4-IN.