PC3T: a signature-driven predictor of chemical compounds for cellular transition

Cellular transitions hold great promise in translational medicine research. However, therapeutic applications are limited by the low efficiency and safety concerns of using transcription factors. Small molecules provide a temporal and highly tuneable approach to overcome these issues. Here, we present PC3T, a computational framework to identify enrich molecules that induce desired cellular transitions, and PC3T was able to consistently identify enrich small molecules that had been experimentally validated in both bulk and single cell datasets. We then predicted and experimentally validated small molecules reprogramming of fibroblasts into hepatocyte-like cells and found that the fibroblasts exhibited epithelial cell morphology and hepatocyte-like specific gene expression pattern after treatment. Overall design: Examine RNA expression profile of MEFs, and MEFs treated by 3 molecules: Carbidopa, CHIR-99021 and LY-364747.