Bulk and single-cell transcriptome profiling of hESC-derived definitive endoderm cells induced by small molecules

Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by including this compound achieves the same differentiation efficiency with a 90% cost reduction. The gene expression profile induced by the compound suggests that it is an inhibitor of the MYC pathway. The proposed in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols. This study characterizes the bulk and single-cell transcriptome profiling of hESC-derived definitive endoderm cells induced by small molecules. Please note that the Single_cell_aggr_* and Single_cell_all.tar.gz files are assocated with Single_cell_36h, Single_cell_Endo_72h, and Single_cell_Meso_72h samples. Please note that the "Bulk_all_cor_names.tsv" contains total 30 data columns. Two sample data for 24 hours of N (N1-38038 and N1-38039) were removed as they were used as controls (stem cells with no treatment) and redundant to include.