PerturbSci-Kinetics: Dissecting key regulators of transcriptome kinetics through scalable single-cell RNA profiling of pooled CRISPR screens

Here we described PerturbSci-Kinetics, a novel combinatorial indexing method for capturing three-layer single-cell readout (i.e., nascent transcriptome, whole transcriptome, sgRNA identities) across hundreds of genetic perturbations. Through PerturbSci-Kinetics profiling of pooled CRISPR screens, we were able to decipher the complexity of RNA dynamics (e.g., synthesis, splicing, and degradation) at both global and gene-specific levels. Our technique opens up the possibility to perform genome-wide perturbations across millions of single cells cost-effectively. A growth screen including 699 gRNAs targeting 228 genes and no-target