PHDs-seq: a large-scale phenotypic screening method for drug discovery through parallel multi-readout quantification

Li J.; Chi J.; Yang Y.Song Z.Yang Y.Zhou X.Liu Y.Zhao Y.

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PHDs-seq: a large-scale phenotypic screening method for drug discovery through parallel multi-readout quantification

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© 2023, The Author(s).High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.

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《cell regeneration》 |2023年第1期|共页
作者
Li J.; Chi J.; Yang Y.Song Z.Yang Y.Zhou X.Liu Y.Zhao Y.;
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State Key Laboratory of Natural and Biomimetic Drugs MOE Key Laboratory of Cell Proliferation and Differentiation Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine College of Future Technology Peking University;

Peking-Tsinghua Center for Life Sciences Peking University;

Plastech Pharmaceutical Technology LtdJiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of General Surgery Peking University Third Hospital;

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正文语种英语
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ABT869; Adipocyte reprogramming; High-throughput screening; PHDs-seq;

PHDs-seq: a large-scale phenotypic screening method for drug discovery through parallel multi-readout quantification

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