PreciCE: Precision engineering of cell fates via data-driven multi-gene control of transcriptional networks

However, current methods for cell fate control are inefficient, imprecise, and rely on laborious trial-and-error. To address these limitations, we present a technology for data-driven multi-gene modulation of transcriptional networks.

We develop bidirectional CRISPR-based tools based on dCas12a, Cas13d, and dCas9 for simultaneously activating and repressing many genes. Due to the vast combinatorial complexity of multi-gene regulation, we introduce a machine learning-based computational algorithm that uses single-cell RNA sequencing data to predict multi-gene perturbation sets for converting a starting cell type into a desired target cell type. By combining these technologies, we establish a unified workflow for data-driven cell fate engineering and demonstrate its efficacy in controlling early stem cell differentiation while suppressing alternative lineages through logic-based cell fate operations.