Kinetics-seq enables comprehensive profiling of single-cell RNA kinetics in vivo to reveal dynamic tumor heterogeneity

Although scRNA-seq has revolutionized cellular profiling, it captures static expression snapshots, lacking direct access to transcriptional dynamics. Here, we present Kinetics-seq, a time-resolved single-cell method that integrates in vivo metabolic labeling strategy with scRNA-seq to construct a comprehensive transcriptional kinetic landscape within tissues.

This approach enables transcriptome-wide quantification of RNA abundance, turnover, synthesis, and degradation rates at single-cell resolution. By incorporating RNA kinetic parameters, Kinetic-seq introduces a dynamic dimension to cellular profiling, revealing heterogeneities not only across cell types but also within individual populations. Through joint modeling of RNA synthesis and degradation rates, Kinetics-seq uncovers gene-specific regulatory strategies and pronounced kinetic diversity among tumor cells.