Beijing Institute of Pharmacology and Toxicology, 100850, Beijing, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
Commun Biol. 2023 Sep 27;6(1):989. 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.
细胞转变在转化医学研究中具有巨大的应用潜力。然而，由于转录因子的效率低和安全性问题，其治疗应用受到限制。小分子提供了一种时间和高度可调的方法来克服这些问题。在这里，我们提出了 PC3T，这是一种计算框架，用于富集诱导所需细胞转变的分子，并且 PC3T 能够一致地富集在批量和单细胞数据集中经过实验验证的小分子。然后，我们预测了小分子将成纤维细胞重编程为肝祖细胞样细胞（HPLCs）。转化后的细胞表现出上皮细胞样形态和 HPLC 样基因表达模式。还观察到了肝的功能，如糖原储存和脂质积累。最后，我们收集并手动整理了一个细胞状态转变资源，其中包含 224 个时间过程基因表达数据集和 153 种细胞类型。我们的框架和数据资源可在 http://pc3t.idrug.net.cn/ 上免费获得。我们相信 PC3T 是促进化学诱导细胞状态转变的有力工具。
