GSE162909
A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion [Single-cell RNA-seq]
Conversion of cellular identity can be achieved safely, without genetic manipulation, by inducing signalling perturbations with chemical compounds to target cell fate-governing transcription factors (TFs). However, chemical-induced cellular conversion currently requires large-scale screening of small compounds, which is time- and labour-intensive. There are no existing computational approaches that facilitate chemical conversion of cell fate. Here, we develop a computational framework (SiPer) to systematically predict chemical compounds specifically targeting desired sets of TFs to direct cellular conversion. This framework integrates a large compendium of chemical perturbation datasets with a network model. We show that SiPer is generally applicable to diverse cellular conversion examples, recapitulating the known chemical compounds and their corresponding protein targets. Furthermore, using chemical compounds predicted by SiPer, we develop a highly efficient protocol for the generation of functional human induced hepatocytes (hiHeps). These results demonstrate that SiPer provides a valuable resource to efficiently identify chemical compounds for cellular conversion. Overall design: 1 sample of hepatic progenitors were analyzed by single-cell RNA-seq.