Biology subjects

Christophe, A.

Publications and source records attributed to Christophe, A..

5 recordsLinked to original sources

bioRxiv2026

SImBA-SiQuAl: a new tool enabling high-content high-throughput phenotypic profiling of 3D microtumours.

Three-dimensional microtumour models such as spheroids are increasingly used in cancer research as they better capture tumour architecture, growth and invasion than conventional two-dimensional cultures. However, robust and accessible tools for quantitative analysis remain limited. Here we present SImBA-SiQuAl, an integrated open-source workflow for high-throughput quantitative phenotyping of 3D spheroids and organoids. The pipeline combines SImBA, an automated image-analysis framework for performant quality-controlled image segmentation and multi-feature extraction from spheroid assays, with SiQuAl, a downstream analysis platform that automatically performs comprehensive statistical and multivariate analyses to reveal phenotypic differences between experimental conditions. In a first case study, we showcase how SImBA-SiQuAl resolves intrinsic invasion phenotypes between cancer cell lines. In a second case study, it quantifies heterogeneous responses in a spheroid drug screening assay. Together, SImBA-SiQuAl provides an effective timely tool for high-throughput, high-content microtumour phenomics in cancer research. MOTIVATION3D-microtumour assays such as spheroids and organoids are increasingly used in preclinical research. These assays generate rich phenotypic imaging data, but automated quantitative analysis remains a major bottleneck. This limits reproducibility, scalability, and broad adoption for large-scale, high-content phenomics studies. Moreover, it impedes comprehensively addressing biologically relevant phenotypic (heterogeneous) responses in e.g. perturbation studies. SImBA-SiQuAl (Spheroid Image Batch Analysis - Simba Quantitative output Analysis) is developed to address this gap by providing an open-source, integrated workflow offering solutions in both the image processing and downstream analysis. Together, this enables in-depth quantitative analysis of 3D microtumour phenotypes across experimental settings.

cancer biology↗

bioRxiv2025

A temporary challenge by tumor cells can lead to a permanent partial-impairment of memory CD8 T cell function

Memory CD8 T cells typically exhibit improved effector functions compared to their naive counterparts. However, under certain activation conditions, such as chronic viral infections or cancer, these cells may develop functional defects. In this study, we compared the functional quality of memory CD8 T cells generated following tumor rejection with those arising from an acute viral infection. We found that tumor-induced (Tum-CD8) memory cells exhibited a distinct phenotype and transcriptomic profile compared with viral-induced (Vir-CD8) memory cells. These memory cells are characterized by the expression of inhibitory receptors and displayed altered functions including reduced IFN{gamma} and TNF production as well as changes in integrin expression. Additionally, the protective capacity of Tum-CD8 memory cells was flawed relative to that of Vir-CD8 memory cells. Importantly, the functional defects of Tum-CD8 persisted upon viral recall. Together, these findings indicate that transient tumoral stimulation can imprint a stable partial exhaustion-like program on memory CD8 T cells.

immunology↗

bioRxiv2023

In silico single-cell metabolism analysis unravels a new transition stage of CD8 T cells 4 days post-infection

CD8 T cell proper differentiation during antiviral responses relies on metabolic adaptations. Herein, we investigated global metabolic activity in single CD8 T cells along an in vivo response by estimating metabolic fluxes from single-cell RNA-sequencing data. The approach was validated by the observation of metabolic variations known from experimental studies on global cell populations, while adding temporally detailed information and unravelling yet undescribed sections of CD8 T cell metabolism that are affected by cellular differentiation. Furthermore, inter-cellular variability in gene expression level, highlighted by single cell data, and heterogeneity of metabolic activity 4 days post-infection, revealed a new transition stage accompanied by a metabolic switch in activated cells differentiating into full-blown effectors.

immunology↗

bioRxiv2023

A screening strategy based on two zebrafish eleuthero-embryo OECD test guidelines for the hazard assessment of chemicals: case of some bisphenol substitutes

The use of efficient screening strategies for the hazard assessment of chemicals is a current challenge to support regulatory requirements. Herein, we combined two eleuthero-embryo assays, a refined Fish Embryo Toxicity assay (OECD TG 236) and the EASZY assay (OECD TG 250), both using transgenic (tg) (cyp19a1b:GFP). The simultaneous performance of both assays provides complementary information about the acute toxicity, developmental effects, and estrogenic activity. A refined EASZY assay is however necessary to obtain accurate EC50. In this work we compared bisphenol A (BPA) and ten of its substitutes. In the refined FET, most of the selected bisphenols were more toxic than BPA, induced developmental effects on zebrafish embryos, some being identified as teratogenic compounds (BPF, BPS-MAE, BPC Cl, 4,4ODP), and ten of them induced GFP intensity. Endocrine activity of the BPs was further investigated in the EASZY assay at concentrations that do not affect the survival and the hatching rates or induce developmental toxicity based on the target concentrations used as previously defined in the refined FET. All bisphenols elicited an estrogenic activity with the notable exception of TCBPA. Most BPs were more estrogenic than BPA, acted as agonist ligands of zfER{beta}2 as shown in zebrafish-specific in vitro reporter gene assay and functional zfERs were required to induce brain aromatase. Interestingly, BPS-MAE and BPS-MPE behave as pro-estrogens as they were unable to transactivate zebrafish ER{beta}2 in vitro but induced brain aromatase in vivo. Overall, the implementation of the zebrafish eleuthero embryo-based screening strategy efficiently provided relevant data contributing to their environmental hazard. It also provides further evidence that bisphenols modulate cyp19a1b expression during early brain development whom potential short and long-term adverse effects need to be addressed. SYNOPSISa zebrafish eleuthero embryo-screening strategy based on OECD TGs was implemented for an efficient hazard assessment of bisphenols revealing that most of them are more toxic and/or estrogenic than BPA

pharmacology and toxicology↗

bioRxiv2018

Leaf economics guides slow-fast adaptation across the geographic range of A. thaliana

The slow-fast continuum describes how resource allocation constrains life-history strategies in many organisms. In plants, it is reflected by a trade-off at the leaf level between the rate of carbon assimilation and lifespan, the so-called Leaf Economics Spectrum (LES). However, it is still unclear how the LES is connected to the slow-fast syndrome, and reflects adaptation to climate. Here, we measured growth, morpho-physiological and life-history traits at both leaf and whole-plant levels in 384 natural accessions of Arabidopsis thaliana. We examined the extent to which the LES continuum parallels the slow-fast continuum, and compared trait variation to neutral genetic differentiation between lineages. We found that the LES is tightly linked to variation in whole-plant functioning, relative growth rate and life history. A genetic analysis further suggested that phenotypic differentiation is linked to the evolution of different slow-fast strategies in contrasted climates. Together, our findings shed light on the physiological bases of the slow-fast continuum, and its role for plant adaptation to climate.

ecology↗