Biology subjects

Taboureau, O.

Publications and source records attributed to Taboureau, O..

5 recordsLinked to original sources

bioRxiv2026

Cell Painting-Based Tool for the Risk Assessment of Mammary Carcinogens and Endocrine Disruptors

Breast cancer is the most common cancer in women worldwide and chemicals disrupting estrogen or progesterone signaling are recognized as potential risk factors. However, chemicals that alter the mammary gland (MG) development and function remain understudied, highlighting the need for additional research in this area. To address this gap, we investigate the relevance of using high-content imaging assays and more specifically, Cell Painting technology to measure cell morphology perturbation caused by chemical exposure and identify morphological features that could characterize mammary carcinogens (MC) risk factors. Using a dataset of MC and non-mammary carcinogens (Non-MC) with Cell Painting profiles from the JUMP-CP dataset, we retrieved 51 compounds: 28 MC, 23 non-genotoxic Non-MC. We characterized the morphological data by non-linear dimensionality reduction (UMAP) and hierarchical clustering. We, then, developed a Guilt-By-Association (GBA) framework comparing multiple configurations of similarity metrics, risk-score aggregation approaches and features representations. Morphological profiles clustered by mechanism of action rather than carcinogenicity label: genotoxic MC produced strong perturbations in endoplasmic reticulum, mitochondria, nucleus, and RNA compartments, whereas hormonally active compounds were indistinguishable from controls, reflecting the lack of functional steroid hormone receptors in the cell line used. Our best GBA configuration achieved an AUC-ROC of 0.630 and an AUC-PR of 0.696. Applied prospectively to endocrine disruptors chemicals, it prioritized clofentezine, 3-methylpyrazole, resorcinol, 2-tert-butyl-4-methoxyphenol, and thiabendazole as candidates for confirmatory testing. This study provides a transparent, interpretable tool for prioritizing chemicals in mammary carcinogenicity assessment, highlights limitations and clarifies where Cell Painting datasets must be complemented by hormone-sensitive models.

bioinformatics↗

bioRxiv2025

Decoding the pituitary gonadotrope regulatory architecture governing the preovulatory surge in vivo

Despite the global burden of female infertility, the molecular control of ovulation remains unclear. Pituitary gonadotropes tune hormonal output to regulate ovarian function, yet the molecular mechanisms that control their function during the sexual cycle remain poorly understood. Using state-of-the-art single-nucleus multiomic profiling of the female rat pituitary across the estrus cycle, we uncover unexpected cyclic epigenetic and transcriptional remodelling in gonadotrope cells, particularly during the preovulatory surge. This plasticity is driven by a biphasic gene regulatory network switch that orchestrates large-scale reorganisation of the secretory machinery. We further demonstrate that, contrary to the prevailing model, the LH surge does not depend on Lhb transcriptional upregulation. Instead, the FSH surge arises from dynamic Fshb transcription mediated by a complex combination of newly identified enhancers and key transcription factors. Overall, our findings define a new molecular framework for gonadotropin surge regulation and provide a foundational resource for understanding female reproductive disorders.

physiology↗

bioRxiv2024

Cell morphology and gene expression: tracking changes and complementarity across time and cell lines

Effective drug discovery relies on combining target knowledge with functional assays and multi-omics data to understand chemicals molecular actions. However, the relationship between cell morphology and gene expression over time and across cell lines remains unclear. To explore this, we analyzed Cell Painting and L1000 data for 106 compounds across three cell lines from osteoblast, lung, and breast tumors (U2OS, A549, and MCF7) at three time points (6h, 24h, 48h) using a 10{micro}M concentration. We found significant time and cell line effects in Cell Painting data, with less pronounced effects in transcriptomics. Using Weighted Gene Co-expression Network Analysis (WGCNA) and enrichment analysis, we identified connections between cell morphology and gene deregulation for chemicals with similar biological effects (e.g., HDAC and CDK inhibitors). These findings suggest that while Cell Painting shows distinct patterns, both technologies offer complementary insights into compound-induced cellular changes, enhancing drug discovery and chemical risk assessment.

bioinformatics↗

bioRxiv2021

Transcriptome analysis of Plasmodium falciparum isolates from Benin reveals specific gene expression associated with cerebral malaria

The host and parasitic factors leading to cerebral malaria (CM) are not yet fully elucidated and CM Plasmodium falciparum isolates transcriptome profile remains largely unknown. Based on RNA-seq data from 15 CM and 15 uncomplicated malaria (UM) children from Benin, we identified an increased ring stage signature in CM parasites. Reduced circulating time may result from a higher adherence ability of CM isolates and consistent with this hypothesis, we measured an overexpression of var genes in CM. var genes domains expression was more restricted in CM isolates compared to UM, reflecting the specific binding to receptors in host brain endothelium capillaries. However, ICAM-1 binding motif was found expressed in both CM and UM, questioning its role in PfEMP1 adhesion to ICAM-1 receptor. UM isolates increased circulation time may also be modulated by a more efficient immune response against infected erythrocytes surface proteins, which we could not demonstrate on our cohort. Identification of deregulated genes involved in adhesion, excluding variant surface antigens, also supports the hypothesis of an increased CM adhesion capacity. Finally, numerous upregulated genes involved in entry into host pathway were found, reflecting a greater erythrocytes invasion capacity of CM parasites.

genomics↗

bioRxiv2018

CBP/EP300-dependent acetylation and stabilization of HSF2 are compromised in the rare disorder, Rubinstein-Taybi syndrome

Cells respond to protein-damaging insults by activating heat shock factors (HSFs), key transcription factors of proteostasis. Abnormal HSF protein levels occur in cancer and neurodegenerative disorders, highlighting the importance of the tight control of HSF expression. HSF2 is a short-lived protein, but it is abundant in the prenatal brain cortex and required for brain development. Here, we reveal that HSF2 is acetylated and co-localized with the lysine-acetyl transferases CBP and EP300 in human brain organoids. Using unbiased, biochemical, cell-imaging, and in silico approaches, we show that CBP/EP300 acetylates HSF2 at specific lysine residues, which promotes HSF2 stabilization, whereas the lysine deacetylase HDAC1 catalyzes its proteasomal degradation. The CBP KIX domain and KlX-recognizing motifs in HSF2 are critical for its interaction with acetylating enzymes. The functional importance of acetylated HSF2 is evidenced in Rubinstein-Taybi syndrome (RSTS), characterized by mutated CBP or EP300. We show that RSTS patient cells exhibit decreased HSF2 levels and impaired heat shock response. The dysregulated HSF pathway in RSTS opens new avenues for understanding the molecular basis of this multifaceted pathology.

developmental biology↗