10.1371/journal.pcbi.1007543 Christopher Barry Christopher Barry Matthew T. Schmitz Matthew T. Schmitz Cara Argus Cara Argus Jennifer M. Bolin Jennifer M. Bolin Mitchell D. Probasco Mitchell D. Probasco Ning Leng Ning Leng Bret M. Duffin Bret M. Duffin John Steill John Steill Scott Swanson Scott Swanson Brian E. McIntosh Brian E. McIntosh Ron Stewart Ron Stewart Christina Kendziorski Christina Kendziorski James A. Thomson James A. Thomson Rhonda Bacher Rhonda Bacher Automated minute scale RNA-seq of pluripotent stem cell differentiation reveals early divergence of human and mouse gene expression kinetics Public Library of Science 2019 transcriptional responses Automated minute scale RNA-seq differentiation transcriptomic response rates transcriptomic response kinetics mouse gene expression kinetics Pluripotent gene expression changes gene expression patterns pluripotent 2019-12-09 18:30:15 Dataset https://plos.figshare.com/articles/dataset/Automated_minute_scale_RNA-seq_of_pluripotent_stem_cell_differentiation_reveals_early_divergence_of_human_and_mouse_gene_expression_kinetics/11343305 <div><p>Pluripotent stem cells retain the developmental timing of their species of origin <i>in vitro</i>, an observation that suggests the existence of a cell-intrinsic developmental clock, yet the nature and machinery of the clock remain a mystery. We hypothesize that one possible component may lie in species-specific differences in the kinetics of transcriptional responses to differentiation signals. Using a liquid-handling robot, mouse and human pluripotent stem cells were exposed to identical neural differentiation conditions and sampled for RNA-sequencing at high frequency, every 4 or 10 minutes, for the first 10 hours of differentiation to test for differences in transcriptomic response rates. The majority of initial transcriptional responses occurred within a rapid window in the first minutes of differentiation for both human and mouse stem cells. Despite similarly early onsets of gene expression changes, we observed shortened and condensed gene expression patterns in mouse pluripotent stem cells compared to protracted trends in human pluripotent stem cells. Moreover, the speed at which individual genes were upregulated, as measured by the slopes of gene expression changes over time, was significantly faster in mouse compared to human cells. These results suggest that downstream transcriptomic response kinetics to signaling cues are faster in mouse versus human cells, and may offer a partial account for the vast differences in developmental rates across species.</p></div>