Biology subjects

Dumont, M.

Publications and source records attributed to Dumont, M..

15 recordsLinked to original sources

bioRxiv2026

Nanoscale identification of organic pigments in biogenic calcite by atom probe tomography

Spatially-resolved mass spectrometry could contribute to the understanding of biological processes. Atom probe tomography (APT) is a technique which could, in principle, fill an analytical gap for nanoscale mass spectrometry. Yet, because of a limited understanding of the process of fragmentation of biomolecules, biological or biochemical interpretation of the obtained data has so far not been successful. Here, we report on analyses of synthetic and biogenic pigmented calcite minerals. The purple coloration of Sphaerechinus granularis sea urchin spines is due to the occlusion of polyhydroxylated naphthoquinone (PHNQ) molecules, mainly spinochrome A, within the calcite phase. Peaks relating to these pigments as well as to other intra-crystalline macromolecules were identified by APT analysis of the purple spine region with comparison to measurements of synthetic calcite single crystals, calcite crystals doped with PHNQ, and the uncoloured (white) region of sea urchin spines. To facilitate the molecular identification of peaks appearing solely in purple-coloured spines, which are possible fragments from PHNQ, we introduce novel APT data filtering techniques based on spatial and temporal correlations in the detection of ions of targeted mass-to-charge state ratios. This allows us to discuss the fragmentation of organic molecules under field conditions and improve the identification of peaks in the mass spectrum, while also determining nanoscale spatial distribution of fragments related to specifically targeted biomolecules in 3D and elucidate the relationship these organic pigment molecules have to the calcite lattice and inorganic elements such as magnesium. The study aims to improve identification of complex molecular structures by APT, including organic molecules, with the potential ability to provide structural information at a near-atomic scale for a range of materials.

biophysics↗

bioRxiv2026

Nanoscale chemical tomography reveals organic and inorganic clusters in fossilised dinosaur tooth

Mineralized dental tissues are formed through biomineralization processes involving the growth and self-organisation of hydroxylapatite (HAP) nanoscale grains. There remain open questions regarding the way elements such as Mg or Na are incorporated in the organic matter between HAP grains or within the grain structure where they influence the nucleation and growth of HAP. Here, mapping the enamel structure and composition of a well-preserved ca. 150-million-year-old Giraffatitan brancai sauropod dinosaur tooth from millimeters down to the near-atomic scale, we reveal the nanoscale accumulation of Mg at HAP grain boundaries, alongside F arising from diagenesis. Within the HAP grains and at HAP grain boundaries organic matter forms clusters that we propose contribute to the fast growth rate of the tooth. Moreover, unexpected Cu3As particles are found across the entire enamel structure. These elements are not in the dentine, that exhibits empty tubules, which suggests that they were integrated during the tooth growth itself. Our multiscale analysis provides new information encouraging to reconsider aspects of the biomineralization and fossilization processes.

paleontology↗

bioRxiv2025

Increased tissue tension caused by depletion of CLDN3 in the non-neural ectoderm causes neural fold fusion defects in chick embryos

Neural tube morphogenesis provides a dynamic setting in which to study epithelial cell behaviours. Members of the claudin family of tight junction proteins regulate apical epithelial cell behaviors at all steps of neural tube development. We discovered that CLDN3, expressed in the non-neural ectoderm but not the neural ectoderm, is required to mediate neural fold fusion in chick embryos, particularly in the spinal region of the embryo. Depleting CLDN3 affects apical protein localization and apical domain morphology. Here, we used live imaging to re-examine the process of neural fold fusion in the cranial and spinal regions of the embryo and assessed biomechanical parameters of the non-neural ectoderm that are dependent on CLDN3. Our live imaging confirmed previous reports that unlike neural fold fusion in the cranial region and posterior neuropore, the spinal region does not depend on progressive fusion driven by "zippering" cell behaviors but instead fuses in a multi-step process where contact occurs simultaneously at multiple points along the anterior-posterior axis. We and others refer to the process of spinal neural fold fusion as "buttoning" to highlight the differences in cell behaviors from those observed during zippering (van Straaten et al., 1993). CLDN3-depletion decreased the rate of progression of neural fold buttoning within the spinal region. Using cell segmentation analyses we confirmed that CLDN3 depletion decreased the apical cell area of cells at the edges of the neural folds but not of lateral cells in the non-neural ectoderm. CLDN3 depletion increased pMLC staining within the apical domain of the cell, coinciding with a decrease in cell area, suggesting increased epithelial tension. Laser ablation studies revealed that the non-neural ectoderm of CLDN3-depleted embryos exhibits higher tension during neural fold fusion. We showed that treatment with the myosin II inhibitor blebbistatin is sufficient to partially rescue the neural fold fusion defects in CLDN3-depleted embryos. This work provides further evidence for the importance of non-neural ectodermal tissue tension in neural fold fusion and suggests that loss of CLDN3 may alter tissue tension through cytoskeletal regulation pathways within the apical domain. This work supports that CLDN3 contributes to neural fold fusion and epithelial tissue tension during neural fold fusion via modifications to the apical cytoskeleton. SummaryWe found that the tight junction protein Claudin-3 (CLDN3) plays a role in regulating tissue tension, by directing actomyosin contraction and apical cell shape/size changes essential for chick neural fold fusion.

developmental biology↗

bioRxiv2025

Thermal acclimation fails to confer a carbon budget advantage to invasive species over natives

Both native and invasive plants can adjust photosynthesis and respiration when exposed to warmer temperatures. However, it is uncertain if invasive plants are more plastic and exhibit higher acclimation to rising temperatures than native ones, a trait that could contribute to their invasive behavior in novel environments. We compared the capacity of a highly invasive palm in central Europe (Trachycarpus fortunei) and two native co-occurring species (Ilex aquifolium and Tilia cordata) to acclimate photosynthesis and respiration to air temperature changes using a two-year-long transplant experiment across Europe (mean temperatures ranging from 8.4 to 21.8{degrees}C). We measured the optimal temperature of photosynthesis (Topt), the assimilation at optimal temperature (Aopt), the thermal breath of photosynthesis (T80), the respiration at 25{degrees}C (R25), the temperature sensitivity of respiration (Q10), and simulated the whole-plant carbon budget. For all species, Topt, Aopt, and T80 increased with warming, while R25 decreased in the native species and Q10 decreased in the invasive species only. Consequently, acclimation enhanced the carbon budget of the invasive and native plants in the warm and hot sites. The invasive palm had a similar or lower acclimation capacity than other species and a lower but constant carbon budget across the European temperature gradient. Our work reveals that not all invasive plants exhibit greater photosynthetic plasticity than native ones, suggesting that temperature-driven enhancement of their carbon budget may play a limited role in future invasion processes.

plant biology↗

bioRxiv2025

Heterochromatin boundaries maintain centromere position, size and number

Centromeres are chromosomal loci that ensure proper chromosome segregation by providing a platform for kinetochore assembly and spindle force transduction during cell division. Human centromeres are defined primarily by a unique chromatin domain featuring the histone H3 variant, Centromere Protein A (CENP-A), that marks a single active centromere locus per chromosome. CENP-A chromatin typically occupies a small subregion of low DNA methylation within multi-megabase arrays of hypermethylated alpha-satellite repeats and constitutive pericentric heterochromatin. However, the mechanisms defining and maintaining precise centromere position and domain size, and the role of the underlying alpha satellite DNA sequence, are poorly characterised. Using an experimentally-induced neocentromere in RPE1 cells, we discovered that the SUV39H1 and H2 methyltransferases tri-methylate H3K9 at neocentromere boundaries to maintain CENP-A domain size independent of DNA methylation or satellite sequences. Furthermore, we found that the CENP-A domain at canonical alpha-satellite-based centromeres is characterized by local depletion of H3K9me3-mediated heterochromatin, coinciding with the DNA methylation dip region. We identified the SETDB1 methyltransferase as key to maintaining H3K9me3 within flanking active higher order alpha satellite arrays while SUV39s and SUZ12 contribute to globally heterochromatinize both alpha satellites and neighbouring repeats. Loss of this heterochromatin boundary results in the progressive expansion of the primary CENP-A domain, erosion of DNA methylation, and the nucleation of new centromeres across alpha satellite sequences. Our study identifies the functional specialization of different H3K9 methyltransferases across centromeric and pericentric domains, crucial for maintaining centromere domain size and number.

genomics↗

bioRxiv2025

Genome-scale transcriptome augmentation during Arabidopsis thaliana photomorphogenesis

Plant photomorphogenesis is a light-induced developmental switch that combines massive reprogramming of gene expression and a general enhancement in RNA Polymerase II activity. Yet, transcriptome analyses have failed to demonstrate a clear tendency toward gene upregulation. To solve this conundrum, we optimized a spike-in RNA-seq experimental and analysis pipeline and reconciled transcriptome dynamics with epigenomic and cytogenetic observations. We found that light induces a two-fold expansion of the transcriptome during Arabidopsis thaliana cotyledon photomorphogenesis, with 94% of the 9,128 differentially expressed genes being upregulated within the first six hours. Transcriptome augmentation was further detected at a similar strength in spike-free RNA-seq datasets from independent laboratories renormalized using stable genes that mimic the spike-in information. On this new basis, reinterpretation of light-mediated gene regulatory pathways revealed a quasi-exclusive positive effect of HY5 and other key light-induced transcription factors at target genes. This new standpoint unveiled the unilateral impact of light on the transcriptome of Arabidopsis cotyledons at the genome scale and opens new avenues for investigating global genome regulation during plant developmental and environmental responses.

plant biology↗

bioRxiv2022

Armed to the teeth: the underestimated diversity in tooth shape in snakes and its relationship to feeding constraints

Teeth are one of the most studied hard tissues in vertebrates. Their structure, composition and shape are related to dietary specialization in many species. At first glance, snake teeth all look similar; conical, sharp, curved. Yet, snakes, like other vertebrates, have very diverse diets that may have affected their shape. We compared the morphology of the teeth of 63 species that cover both the phylogenetic and dietary diversity of snakes. We predicted that prey properties play a role in shaping snakes teeth along with their feeding behavior. Limblessness combined to the peculiar feeding behavior of snakes impose strong functional constraints on their teeth, especially during arboreal or aquatic feeding. Our results show that prey hardness, foraging substrate and the main feeding constraint are drivers of tooth shape, size, and curvature. We highlight two main morphotypes: long, slender, curved with a thin layer of hard tissue for snakes that need a good grip on their prey and short, stout, less curved teeth in snakes that eat hard or long prey. Our study demonstrates the diversity of tooth morphology in snakes and the need to investigate the underlying functional implications to better understand the evolution of teeth in vertebrates.

evolutionary biology↗

bioRxiv2022

High-frequency longitudinal white matter diffusion- & myelin-based MRI database: reliability and variability

Assessing the consistency of quantitative MRI measurements is critical for inclusion in longitudinal studies and clinical trials. Intraclass coefficient correlation and coefficient of variation were used to evaluate the different consistency aspects of diffusion- and myelinbased MRI measures. Multi-shell diffusion and inhomogeneous magnetization transfer datasets were collected from twenty healthy adults at a high-frequency of five MRI sessions. The consistency was evaluated across whole bundles and the track-profile along the bundles. The impact of the fiber populations on the consistency was also evaluated using the number of fiber orientations map. For whole and profile bundles, moderate to high reliability of diffusion and myelin measures were observed. We report higher reliability of measures for multiple fiber populations than single. The overall portrait of the most consistent measurements and bundles drawn from a wide range of MRI techniques presented here will be particularly useful for identifying reliable biomarkers capable of detecting, monitoring and predicting white matter changes in clinical applications and has the potential to inform patient-specific treatment strategies. Key pointsO_LIReliability and variability are excellent to good for DWI measurements, and good to moderate for MT measures for whole bundles and along the bundles. C_LIO_LIThe number of fiber populations affects the reliability and variability of the MRI measurements. C_LIO_LIThe reliability and variability of MRI measurements are also bundle dependent. C_LI

neuroscience↗

bioRxiv2022

Molecular origins of genome instability following a single chromosome mis-segregation event

Chromosome instability (CIN) is the most common form of genome instability and is a hallmark of cancer. CIN invariably leads to aneuploidy, a state of karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found that aneuploid cells experience DNA replication stress in their first S-phase and precipitate in a state of continuous CIN. This generates a repertoire of genetically diverse cells that can either continue proliferating or stop dividing. Cycling aneuploid cells display lower karyotype complexity compared to the arrested ones and increased expression of DNA repair signatures. Interestingly, the same signatures were upregulated in highly-proliferative cancer cells, which might enable them to proliferate despite the disadvantage conferred by aneuploidy-induced CIN. Altogether, our study reveals the short-term origins of CIN following aneuploidy and indicates the aneuploid state of cancer cells as a point mutation-independent source of genome instability, providing an explanation for aneuploidy occurrence in tumors.

cell biology↗

bioRxiv2021

Kronos scRT: a uniform framework for single-cell replication timing analysis

Mammalian genomes are replicated in a cell-type specific order and in coordination with transcription and chromatin organization. Although the field of replication is also entering the single-cell era, current studies require cell sorting, individual cell processing and have yielded a limited number (<100) of cells. Here, we have developed Kronos scRT (https://github.com/CL-CHEN-Lab/Kronos_scRT), a software for single-cell Replication Timing (scRT) analysis. Kronos scRT does not require a specific platform nor cell sorting, allowing the investigation of large datasets obtained from asynchronous cells. Analysis of published available data and droplet-based scWGS data generated in the current study, allows exploitation of scRT data from thousands of cells for different mouse and human cell lines. Our results demonstrate that, although most cells replicate within a close timing range for a given genomic region, replication can also occur stochastically throughout S phase. Altogether, Kronos scRT allows investigating the RT program at a single-cell resolution for both homogeneous and heterogeneous cell populations in a fast and comprehensive manner.

genomics↗

bioRxiv2020

CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy

Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity to prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of the centromere-specific histone H3 variant CENP-A in safeguarding DNA replication of alpha-satellite repeats to prevent structural aneuploidy. Rapid removal of CENP-A in S-phase, but not other cell cycle stages, caused accumulation of R-loops with increased centromeric transcripts, and interfered with replication fork progression. Replication without CENP-A causes recombination at alpha-satellites in an R-loop-dependent manner, unfinished replication and anaphase bridges. In turn, chromosome breakage and translocations arise specifically at centromeric regions. Our findings provide insights into how specialized centromeric chromatin maintains the integrity of transcribed noncoding repetitive DNA during S-phase. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/277103v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@4e6dc4org.highwire.dtl.DTLVardef@1089c90org.highwire.dtl.DTLVardef@5ee5c2org.highwire.dtl.DTLVardef@3e300d_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

CENP-A overexpression drives distinct cell fates depending on p53 status

Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays and single-cell RNA-sequencing over time, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. But, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential precursor for tumour cell invasion and metastasis. Thus, CENP-A overexpression drives distinct cell fates depending on p53 status, with important implications for tumour evolution.

cancer biology↗

bioRxiv2020

The Biomechanical Basis of Biased Epithelial Tube Elongation

During lung development, epithelial branches expand preferentially in longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How this bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme, of preferential turn-over of the extracellular matrix at the bud tips, and of FGF signalling. There is also no evidence for actin-rich filopodia at the bud tips. Rather, we find epithelial tubes to be collapsed during early lung and kidney development, and we observe fluid flow in the narrow tubes. By simulating the measured fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis. Summary StatementWe systematically analysed the requirements for biased elongating outgrowth of epithelial tubes during lung and kidney development, and provide evidence that fluid-flow induced shear stress drives their biased elongation.

developmental biology↗

bioRxiv2019

Free water in white matter differentiates MCI and AD from control subjects

Recent evidence show that neuroinflammation plays a role in many neurological diseases including mild cognitive impairment (MCI) and Alzheimers disease (AD), and that free water (FW) modeling from clinically acquired diffusion MRI (DTI-like acquisitions) can be sensitive to this phenomenon. This FW index measures the fraction of the diffusion signal explained by isotropically unconstrained water, as estimated from a bi-tensor model. In this study, we developed a simple FW processing pipeline that uses a safe white matter (WM) mask without gray matter (GM)/CSF partial volume contamination (WMsafe) near ventricles and sulci. We investigated if FW inside the WMsafe mask, including and excluding areas of white matter damage such as white matter hyperintensities (WMHs) as shown on T2 FLAIR, computed across the whole white matter could be indicative of diagnostic grouping along the AD continuum. After careful quality control, 81 cognitively normal controls (NC), 103 subjects with MCI and 42 with AD were selected from the ADNIGO and ADNI2 databases. We show that MCI and AD have significantly higher FW measures even after removing all partial volume contamination. We also show, for the first time, that when WMHs are removed from the masks, the significant results are maintained, which demonstrates that the FW measures are not just a byproduct of WMHs. Our new and simple FW measures can be used to increase our understanding of the role of inflammation-associated edema in AD and may aid in the differentiation of healthy subjects from MCI and AD patients.

neuroscience↗

bioRxiv2017

A (blue) light in the dark: Blue light modulates oscillatory alpha activity in the occipital cortex of totally visually blind individuals with intact non-visual photoreception

The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) marked a major shift in our understanding of how light is processed by the mammalian brain. These ipRGCs influence multiple functions not directly related to vision such as the synchronization of circadian rhythmicity, pupil constriction, the regulation of alertness and sleep, as well as the modulation of cognition. More recently, it was demonstrated that ipRGCs may also contribute to basic visual functions. The impact of ipRGCs on visual functions, independently of image forming photoreceptors, remains however difficult to isolate, particularly in humans. We previously showed that exposure to intense monochromatic blue light (465nm) induced awareness of light in a forced choice task in three rare totally visually blind individuals without detectable rod and cone function, but who retained non-visual responses to light, very likely via ipRGCs. The neural foundation of such light awareness in the absence of conscious vision is unknown, however. In this study, we characterized the brain activity of these three rare participants using electroencephalography (EEG), and demonstrate that unconsciously perceived light triggers an early and reliable transient desynchronization (i.e. decreased power) of the alpha EEG rhythm (8-14 Hz) over the occipital cortex. These results provide compelling insight into how ipRGC may contribute to transient changes in ongoing brain activity. They suggest that occipital alpha rhythm synchrony, which is typically linked to the visual system, is modulated by ipRGCs photoreception; a process that may contribute to the awareness of light in those blind individuals.

neuroscience↗