Biology subjects

Fournier, L.

Publications and source records attributed to Fournier, L..

5 recordsLinked to original sources

bioRxiv2026

Environmental risk reshapes high-confidence schizophrenia risk genes during a developmental window of vulnerability

Rare coding variants and environmental exposures such as early-life stress contribute to schizophrenia risk, but whether environmental adversity alters the expression of genetically implicated genes remains unclear. Combining the limited bedding and nesting (LBN) model of early-life stress (ELS) with 24-plex single-cell mFISH registered to the Allen Mouse Brain Atlas, we profiled the ten genes identified in the original SCHEMA study, the complement gene C4b and activity markers in 1.29 million cells across four postnatal ages. Whole-brain risk-gene upregulation was greatest at postnatal day 21 (P21), with region- and cell-type-selective effects that prominently involved the hypothalamus. Sp4 and Cacna1g showed distinct temporal responses: Sp4 increased at P21 and decreased at P90 in hypothalamic oligodendrocytes, whereas Cacna1g decreased at P10. ELS-associated C4b upregulation extended across neuronal and glial populations, including oligodendrocytes and OPCs. Across regional cell types, P10 C4b effects were positively correlated with P21 Grin2a effects. These findings suggest that ELS perturbs the developmental expression of genes implicated in schizophrenia, identifying potential molecular links between environmental adversity and genetic vulnerability.

neuroscience↗

bioRxiv2026

Resolving context-specific protein-protein interactomes forbiological discovery and therapeutic target prioritisation

Protein function is shaped by cellular context, yet most protein representations and interaction maps remain context-agnostic. Here we present ProtScape, a multiscale graph-learning framework integrating global protein interactions, cell-type gene expression and protein language models to learn context-specific representations and infer interactomes across more than 200 cell types. ProtScape substantially outperforms existing approaches in interaction reconstruction, increasing the area under the precision-recall curve by 40 percentage points. Its predicted interactions were supported by held-out continuous STRING global evidence, while its representations recovered higher-order protein organisation. In patient-derived amyotrophic lateral sclerosis motor neurons, ProtScape revealed stage-specific network changes implicating RAB-dependent trafficking as a candidate early disease mechanism. In Parkinson's disease, it recovered clinically supported therapeutic targets from a proteome-wide search space 16-fold smaller than that required by competing representations. Together, ProtScape provides a scalable framework for translating context-specific interactome organisation into experimentally testable disease mechanisms and therapeutic hypotheses.

bioinformatics↗

bioRxiv2026

The roles and synthesis of inorganic polyphosphate in Bacillus cereus

Inorganic polyphosphate (polyP) is a universally conserved biopolymer central to bacterial stress survival, yet understanding of its roles derives almost entirely from Gram-negative models in which polyP accumulates intracellularly following nutrient downshift. We examined polyP metabolism in the Gram-positive spore-forming bacterium Bacillus cereus using deletions of the polyP kinases PPK1 and PPK2 and the exopolyphosphatase PPX. Intracellular polyP synthesis required PPK1 and was opposed by PPX and PPK2: ppx mutants accumulated polyP in sporulation medium by 24 hours, ppx ppk2 double mutants accumulated more, and no ppk1 mutant accumulated any. A ppk1 ppx double mutant could not be generated, suggesting that unopposed PPK2 activity is lethal. Unlike Escherichia coli and Pseudomonas aeruginosa, B. cereus did not accumulate polyP after shift to minimal medium, increasing only modestly in stationary phase. Fluorescence and transmission electron microscopy localized intracellular polyP to electron-dense granules within ribosome-depleted cytoplasm. Cells bearing these granules remained membrane-intact yet failed to resume growth over 8 hours in rich medium, leading us to propose that polyP drives ribosome sequestration into condensates and a hibernation-like state. Unexpectedly, B. cereus also released close to 100{micro}M polyP extracellularly during late stationary phase, even in a ppk1 ppk2 mutant lacking both known synthetases. Extracellular polyP resisted hydrolysis by purified PPX even after deproteinization, indicating an atypical structure. Bacillus thuringiensis and Bacillus anthracis released similar amounts of extracellular polyP. Together these results identify two distinct polyP pools in the B. cereus group: a PPK1-dependent intracellular pool and an extracellular pool made by an uncharacterized pathway. ImportanceBacillus cereus is a spore-forming bacterium that causes foodborne illness and persists in soil and food-processing environments, where survival depends on managing phosphate and energy reserves during starvation. Inorganic polyphosphate (polyP), an ancient polymer used by nearly all cells to withstand stress, has been studied almost entirely as a molecule stored inside bacteria. We show that Bacillus cereus maintains two separate polyP pools. The internal pool is made by a known enzyme (PPK1) and is associated with dormant cells whose protein-making machinery appears to be packed away. The external pool is made without any known polyP-synthesizing enzyme, pointing to a novel polyP synthesis pathway that is shared with the close relatives Bacillus thuringiensis and Bacillus anthracis.

microbiology↗

bioRxiv2026

Topology-aware reconstruction of cellular state landscapes from microscopy using self-supervised learning

Morphology and spatial organisation provide complementary readouts of cellular state. However, reconstructing continuous cellular state landscapes from imaging data remains challenging, particularly in dense biological cultures. Here we present SI-SimCLR, a spatially informed self-supervised learning framework that learns biologically informative representations directly from fluorescence microscopy images without requiring segmentation or manual annotation. Combined with a graph-based partial optimal transport framework, SI-SimCLR enables reconstruction of cellular phenotypic landscapes from static imaging data, revealing how phenotypic substates are organised and connected. To establish and validate this framework, we generated a multimodal dataset of human iPSC-derived astrocytes using high-content imaging and matched bulk transcriptomics. SI-SimCLR resolved distinct interconnected astrocyte substates associated with disease and inflammatory states. ALS astrocytes occupied constrained regions of the morphological landscape. Strikingly, morphology and transcriptomics captured distinct and complementary aspects of astrocyte state variation.Together, our framework establishes a scalable and annotation-free strategy for reconstructing cellular phenotypic landscapes from microscopy data, enabling analysis of cellular heterogeneity, landscape connectivity and phenotypic responses across biological systems.

bioinformatics↗

bioRxiv2017

Correct laminar positioning in the neocortex influences proper dendritic and synaptic development

The neocortex is a six-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down Dcx, a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines and functional glutamatergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.

neuroscience↗