Biology subjects

De Meester, E.

Publications and source records attributed to De Meester, E..

5 recordsLinked to original sources

bioRxiv2026

LiteVax-adjuvanted influenza vaccine induces transient interferon-driven innate activation and accelerates early IgG3 responses in older adults

Vaccine immunogenicity declines with age due to immunosenescence, underscoring the need for improved adjuvants. LiteVax Adjuvant (LVA), a squalane-in-water emulsion containing carbohydrate fatty-acid monosulphate esters, has shown potential to enhance influenza vaccine responses, but its mechanisms in humans remain unclear. We performed a longitudinal systems vaccinology study in 56 younger (18-45 years) and older ([≥]60 years) adults receiving a quadrivalent influenza vaccine with or without LVA. Multi-omics analyses, including bulk and single-cell transcriptomics, flow cytometry, and serology, revealed that LVA induced a rapid, transient interferon-driven innate response, primarily in monocytes, associated with enhanced antigen processing and dendritic cell to T cell interactions. LVA promoted differentiation of influenza-specific CD4+ T cells toward CD45RO+ memory phenotypes, accelerated early IgG3 antibody responses, and increased IgG-producing plasmablast frequencies without affecting overall antibody magnitude. Importantly, LVA reduced age-related differences in early immune responses, improving response quality and supporting vaccine performance in older adults.

immunology↗

bioRxiv2026

Predicting subclonal TP53 mutations from tumor spatial transcriptomics data using a graph convolutional neural network

Spatial transcriptomics (ST) has revolutionized our understanding of tumor biology but inherently lacks information on the upstream somatic driver mutations. We developed a spatially-aware graph convolutional neural network (MuT-GCNN) that infers TP53 clones directly from ST data. MuT-GCNN was trained on virtual ST slides with clones simulated from a large collection of existing RNA and matched DNA sequencing data. The model is highly performant with precision and recall values exceeding 95% in most analysed cancer types. It is sensitive for single hit mutations and is primarily informed by the expression of p53 signalling genes in cancer cells. After demonstrating the potential of the model on publicly available squamous cell carcinoma (SCC) data, a direct validation was performed using ST and matched DNA sequencing from serial slices obtained from 4 cutaneous SCC samples. With the increasing availability of ST data and upcoming ST atlases, MuT-GCNN can unveil the location of (sub)clonal alterations in TP53, the most frequently mutated gene in human cancer.

cancer biology↗

bioRxiv2026

Integrated single-cell analysis reveals interferon-driven immune signatures in a DENV1 human infection model.

Dengue virus infection triggers complex innate and adaptive immune responses, yet the molecular mechanisms that shape early antiviral immunity remain incompletely defined. We performed longitudinal single-cell multi-omics profiling of peripheral blood mononuclear cells from four flavivirus-naive adults experimentally infected with DENV-1, integrating 5' scRNA-seq with paired surface proteomics. Across 95,841 high-quality cells collected at baseline and on days 8 and 10 post-infection, we observed a strong interferon-driven transcriptional response accompanied by marked immune-cell redistribution, including expansion of monocytes and transient reductions in dendritic cells and double-negative T cells. Cytotoxic and helper lymphocyte populations, particularly naive, central memory, and effector memory CD8 T cells, showed extensive crosstalk with monocytes and NK cells, reflecting coordinated cytokine production and cytotoxic activation. Early B cell activation was evident through increased immunoglobulin gene expression. Innate sensing pathways, including RIG-I and Toll-like signaling, were activated across NK, T, and B cell subsets, while also demonstrating enrichment of antigen processing and apoptosis programs. Pro-inflammatory and cytotoxic signatures peaked at day 8, supported by broad upregulation of interferon-stimulated, pro-apoptotic, and regulatory genes. Together, these findings define a robust IFN-driven antiviral state and coordinated activation of immune cell subsets, providing new insights into the immune dynamics of primary dengue infection. ImportanceDengue virus infects millions of people each year, but the early immune events that shape disease outcomes are still unclear. Most studies measure average responses across all blood cells, which hides how individual cell types react. By tracking thousands of single immune cells from volunteers infected with dengue virus under controlled conditions, we show how the immune system rapidly reorganizes during the first days of infection. Many cell types activate antiviral programs, communicate with one another, and shift their behavior in a coordinated way, driven by strong interferon activity. These results provide a clearer view of how early immune responses unfold in humans and identify cellular processes that may influence who develops more severe illness.

microbiology↗

bioRxiv2023

Genome-wide methylome stability and parental effects in the worldwide distributed Lombardy poplar

BackgroundDespite the increasing number of epigenomic studies in plants, little is known about the forces that shape the methylome in long-lived woody perennials. The Lombardy poplar offers an ideal opportunity to investigate the impact of the individual environmental history of trees on the methylome. ResultsWe present the results of three interconnected experiments on Lombardy poplar. In the first experiment, we investigated methylome variability during a growing season and across vegetatively reproduced generations. We found that ramets collected over Europe and raised in common conditions have stable methylomes in symmetrical CG-contexts. In contrast, seasonal dynamics occurred in methylation patterns in CHH-context. In the second experiment, we investigated whether methylome patterns of plants grown in a non-parental environment correlate with the parental climate. We did not observe a biological relevant pattern that significantly correlates with the parental climate. Finally, we investigated whether the parental environment has persistent carry-over effects on the vegetative offsprings phenotype. We combined new bud set observations of three consecutive growing seasons with former published bud set data. Using a linear mixed effects analysis, we found a statistically significant but weak short-term, parental carry-over effect on the timing of bud set. However, this effect was negligible compared to the direct effects of the offspring environment. ConclusionsGenome-wide cytosine methylation patterns in symmetrical CG-context are stable in Lombardy poplar and appear to be mainly the result of random processes. In this widespread poplar clone, methylation patterns in CG-context can be used as bio-markers to infer a common ancestor and thus to investigate the recent environmental history of a specific Lombardy poplar. The Lombardy poplar shows high phenotypic plasticity in a novel environment which enabled this clonal tree to adapt and survive all over the temperate regions of the world.

genomics↗

bioRxiv2020

ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation.

Loss-of-function of ADAR1 causes the severe autoinflammatory disease Aicardi-Goutieres Syndrome (AGS). ADAR1 converts adenosines into inosines within double-stranded (ds) RNA. This process called A-to-I editing masks self-dsRNA from detection by the antiviral dsRNA sensor MDA5. ADAR1 binds to dsRNA in both the canonical A-form and in the poorly defined Z-conformation (Z-RNA). Mutations in the Z-RNA binding Z-domain of ADAR1 are common in AGS patients. How loss of ADAR1/Z-RNA interaction contributes to disease development is unknown. Using ADAR1 Z-domain mutant human cells and knock-in mice, we demonstrate that abrogated binding of ADAR1 to Z-RNA leads to reduced A-to-I editing of dsRNA structures formed by pairing of inversely oriented SINEs. As a result, ADAR1 Z-domain mutant human cells and transgenic mice develop a spontaneous MDA5-dependent immune response. This shows that the interaction between ADAR1 and Z-RNA restricts sensing of self-dsRNA and prevents AGS development.

immunology↗