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Cell morphology and gene expression: tracking changes and complementarity across time and cell lines
Vanille Lejal1, David Rouquié2, Olivier Taboureau1
1Université Paris Cité, Inserm U1133, CNRS UMR 8251, Paris, France.
Toxicology and Applied Pharmacology
|August 22, 2025
Summary
Cell Painting and L1000 data reveal how chemical exposure alters cell structure and gene expression. These complementary methods enhance drug discovery by linking morphological changes to molecular effects.
Area of Science:
- Chemical biology
- Genomics
- Cellular imaging
Background:
- Drug discovery requires integrating target knowledge, functional assays, and multi-omics data.
- The interplay between chemical-induced changes in cell morphology and gene expression over time and across cell lines is not well understood.
Purpose of the Study:
- To investigate the relationship between cell morphology changes (Cell Painting) and gene expression deregulation (L1000) following chemical exposure.
- To explore these relationships across different cell lines and time points.
Main Methods:
- Analysis of Cell Painting and L1000 data for 106 compounds across U2OS, A549, and MCF7 cell lines at 6, 24, and 48 hours.
- Utilized Weighted Gene Co-expression Network Analysis (WGCNA) and enrichment analysis to identify correlations.
Main Results:
- Observed significant, time- and cell line-specific differences in cellular structure organization via Cell Painting.
- Transcriptomic responses showed less variability compared to morphological changes.
- Identified links between cell morphology and gene deregulation for compounds with similar biological actions (e.g., HDAC and CDK inhibitors).
Conclusions:
- Cell Painting provides distinct patterns of cellular response to chemical exposure.
- Cell Painting and L1000 data offer complementary insights into compound effects.
- These integrated approaches can improve drug discovery and chemical risk assessment by connecting phenotypic and molecular changes.
Keywords:
CDK inhibitorsCell linesCell paintingChemical risk assessmentHDAC inhibitorsL1000Time exposureMore Related Videos
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