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


ABSTRACT: 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.

SUBMITTER: Han L 

PROVIDER: S-EPMC10533498 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Han Lu L   Song Bin B   Zhang Peilin P   Zhong Zhi Z   Zhang Yongxiang Y   Bo Xiaochen X   Wang Hongyang H   Zhang Yong Y   Cui Xiuliang X   Zhou Wenxia W  

Communications biology 20230927 1


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  ...[more]

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