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

• Published in: Communications biology Vol. 6; no. 1; pp. 989 - 11
• Main Authors: Han, Lu, Song, Bin, Zhang, Peilin, Zhong, Zhi, Zhang, Yongxiang, Bo, Xiaochen, Wang, Hongyang, Zhang, Yong, Cui, Xiuliang, Zhou, Wenxia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/91; 631/114/2413; 631/532/2435; 631/553/1833; 96/100; Biology; Biomedical and Life Sciences; Cytology; Epithelial cells; Fibroblasts; Gene expression; Glycogen; Life Sciences; Liver; Progenitor cells; Therapeutic applications; Transcription factors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-05225-y

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 tunable approach to overcome these issues. Here, we present PC3T, a computational framework to enrich molecules that induce desired cellular transitions, and PC3T was able to consistently enrich small molecules that had been experimentally validated in both bulk and single-cell datasets. We then predicted small molecule reprogramming of fibroblasts into hepatic progenitor-like cells (HPLCs). The converted cells exhibited epithelial cell-like morphology and HPLC-like gene expression pattern. Hepatic functions were also observed, such as glycogen storage and lipid accumulation. Finally, we collected and manually curated a cell state transition resource containing 224 time-course gene expression datasets and 153 cell types. Our framework, together with the data resource, is freely available at http://pc3t.idrug.net.cn/ . We believe that PC3T is a powerful tool to promote chemical-induced cell state transitions. PC3T is an in silico chemical screening pipeline to identify small-molecule treatments that induce cell state transitions for any given initial and terminal state or any intermediate state in the cell transition trajectory.