Biology subjects

Clement, R.

Publications and source records attributed to Clement, R..

12 recordsLinked to original sources

bioRxiv2026

System-level regulation of hierarchical transitions in a tumour lineage

The fundamental principles defining how cell state transitions are regulated along a tumour lineage to determine its cellular composition remain unclear. Here, we investigate how such transitions are controlled in a reductionist hierarchical brain tumour model. Quantitative analysis of 3D transition maps revealed that the differentiation of cancer stem cells (CSCs) into transit amplifying progenitors (TAPs) depends on the identity of their immediate neighbours. This is embodied in a transition rule that quantitatively predicts the probability to differentiate as a function of the proportion of TAP neighbours. Integrated into 3D simulations of tumour growth, this rule spontaneously recapitulates spatial segregation of CSCs in clusters and their stable proportion. We further show in vivo that CSC clustering protects the CSC pool from depletion driven by TAPs. We identify an EGFR-mediated relay mechanism that propagates the CSC-to-TAP transition across CSC clusters. In CSCs, the LRIG1-like EGFR inhibitor Kekkon1 dampens this propagation, ensuring continuous replenishment of the CSC pool. Collectively, these findings show how local fate regulation drives emergent segregation which in turn constrains CSC differentiation dynamics. This provides a conceptual framework to understand and exploit the tumours intrinsic differentiation potential by manipulating the determinants of its system-level features.

cancer biology↗

bioRxiv2025

annoSnake: a Snakemake workflow for taxonomic and functional annotation of metagenomes and metagenome-assembled genomes (MAGs)

Omic technologies revolutionised research in microbiomics and helped decipher the complex community structure of gut microbiota, each comprising hundreds of species of bacteria, archaea, and protists. Even as sequencing costs decrease, understanding these communities remains a challenge. Here, we introduce annoSnake, a Snakemake workflow that facilitates taxonomic and functional annotation of metagenomes and metagenomic-assembled genomes (MAGs). This user-friendly and highly flexible workflow integrates state-of-the-art software packages, taking raw sequencing reads, assembling them into contigs, assigning taxonomies and annotating them using various popular protein databases. The workflow handles paired-end as well as interleaved read data, and provides publication-ready figures and tables for downstream analysis. annoSnake, as all Snakemake workflows, is highly scalable, reproducible, and portable, enabling execution across diverse high-performance computing environments with remarkable efficiency.

bioinformatics↗

bioRxiv2025

Fast calcium-dependent reorientation of motile cilia basal bodies in the simple metazoan, Trichoplax.

Ciliary-based animal locomotion relies on the spatially coordinated beating of motile cilia to displace the body in liquid environments or across solid surfaces. The orientation of ciliary beating largely depends on the rotational polarity of the basal body, which in most animals is fixed and controlled by cues linked to the main body axes. The small marine animal Trichoplax exploits the beating of motile cilia in its lower epithelium to crawl on substrates. However, Trichoplax lacks defined body axes and exhibits rapid changes in body shape and direction of movement, thus raising the question of what controls the orientation and reorientation of ciliary beating. We show here that the basal bodies of the cilia in the lower epithelium of Trichoplax are oriented along the direction of the animal movements, and that they change their orientation throughout the lower epithelium in a few seconds time when the animal modifies its shape or changes direction following external mechanical stimuli. We also show that Ca2+ is required for fast basal body reorientation. Such rapid ciliary basal body reorientation has never been observed in metazoans before. Thus, our results identify a previously undescribed mechanism underlying directional motility in a metazoan and shed light on its subcellular determinants, bridging the scale between intra-cellular ciliary machinery and animal movement.

cell biology↗

bioRxiv2025

Conservation strategy insights for three protected Phengaris butterflies combining genetic and landscape analyses

Biodiversity loss is accelerating globally, with insects among the most affected taxa. Wetlands, crucial ecosystems providing essential services, have experienced significant decline due to agricultural intensification and habitat destruction. These changes threaten species that rely on wetland habitats, such as the Phengaris butterflies, which exhibit complex ecological dependencies on specific host plants and ant species. Their populations are structured into metapopulations, where connectivity between habitat patches plays a crucial role in species persistence. This study focuses on population genomics and landscape analysis of three Phengaris species (P. alcon, P. nausithous, P. teleius) in the Bugey Mountain Massif, France, with the aim of developing a conservation strategy. Using ddRAD sequencing, we analyzed genetic diversity, population structure, and gene flow across multiple localities, revealing distinct population clusters with varying degrees of connectivity. Despite some populations exhibiting high genetic diversity levels, others demonstrate low heterozygosity and signs of genetic isolation, emphasizing conservation concerns. Migration estimates and resistance mapping further identified key dispersal corridors and isolated patches requiring targeted interventions. Our findings support metapopulation conservation strategies that prioritize maintaining connectivity, enhancing degraded patches, and identifying new potential habitats. By combining genomic and landscape data, we propose an evidence-based approach to conservation planning, facilitating adaptive management for Phengaris species. This study provides a practical framework for habitat restoration and corridor management in fragmented ecosystems, ensuring long-term species resilience in rapidly changing landscapes.

evolutionary biology↗

bioRxiv2024

Wings expansion in Drosophila melanogaster

During their final transformation, insects emerge from the pupal case and deploy their wings within minutes. The wings deploy from a compact origami structure, to form a planar, rigid and functional blade that allows the insect to fly. The deployment is powered by a rapid increase in internal pressure, and by the subsequent flow of hemolymph into the deployable wing structure. Using a combination of imaging techniques, we characterize the internal and external structure of the wing in Drosophila melanogaster, the unfolding kinematics at the organ scale, and the hemolymph flow during deployment. We find that beyond the mere unfolding of the macroscopic folds, wing deployment also involves an expansion of cell surface and the unfolding of microscopic wrinkles in the cuticle enveloping the wing. A quantitative computational model, incorporating mechanical measurements of the viscoelastic properties and microstructure of the wing, predicts the existence of an operating point for deployment and captures the dynamics of expansion. This model suggests that insects exploit material and geometric nonlinearities to achieve rapid and efficient reconfiguration of soft deployable structures.

biophysics↗

bioRxiv2023

Traumatic brain injury modifies adult hippocampal neural stem cell fate to promote neurogenesis at the cost of astrogliogenesis.

Moderate Traumatic brain injury (TBI) can result in long-lasting changes in brain function. Although frequently spared from the acute primary injury, the hippocampus becomes affected during a secondary phase that takes place hours, or even days, after TBI, contributing to cognitive deficits. The hippocampus is one of the few brain areas in the adult brain harboring native neural stem cells (NSCs) that continue to generate new neurons (neurogenesis), and to a lesser extent new astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, very little is known about how TBI may affect hippocampal astrogliogenesis. Here, we aimed to assess how TBI affects hippocampal NSCs and their subsequent commitment to the neuronal or astroglial lineages. Using a controlled cortical impact model of TBI, single cell RNA sequencing and spatial transcriptomics, we observed a cell population-specific increase in NSC-derived neuronal cells and a decrease in NSC-derived astrocytic cells. These cellular changes were associated with cell-population specific changes in gene expression and dysplasia within the dentate gyrus. Overall, our findings support the conclusion that TBI modifies adult hippocampal NSC fate to promote neurogenesis at the cost of astrogliogenesis, and highlights specific cell populations as possible targets to counteract the changes induced by TBI in the hippocampus.

neuroscience↗

bioRxiv2020

RhoA- and Ran-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes.

Mammalian oocyte meiotic divisions are highly asymmetric and produce a large haploid gamete and two small polar bodies. This relies on the ability of the cell to break symmetry and position its spindle close to the cortex before the anaphase occurs. In metaphase II arrested mouse oocytes, the spindle is actively maintained close and parallel to the cortex, until the fertilization triggers the sister chromatids segregation and the rotation of the spindle. The latter must indeed reorient perpendicular to the cortex to enable the cytokinesis ring closure at the base of the polar body. However, the mechanisms underlying symmetry breaking and spindle rotation have remained elusive. In this study, we show that the spindle rotation results from two antagonistic forces. First, an inward contraction of the cytokinesis furrow dependent on RhoA signaling and second, an outward attraction exerted on both lots of chromatids by a RanGTP dependent polarization of the actomyosin cortex. By combining live segmentation and tracking with numerical modelling, we demonstrate that this configuration becomes unstable as the ingression progresses. This leads to spontaneous symmetry breaking, which implies that neither the rotation direction nor the lot of chromatids that eventually gets discarded are biologically predetermined.

developmental biology↗

bioRxiv2020

The SCF/KIT pathway implements self-organised epithelial patterning by cell movement

How individual cell behaviours lead to the emergence of global patterns is poorly understood. In the Xenopus embryonic epidermis, multiciliated cells (MCCs) are born in a random pattern within an inner mesenchymal layer, and subsequently intercalate at regular intervals into an outer epithelial layer. Using both experiments and mathematical modelling, we show that this transition from chaotic to ordered distribution relies on mutual repulsion among motile immature MCCs, and affinity towards outer-layer intercellular junctions. Consistently, ARP2/3-mediated actin remodelling is required for MCC pattern emergence. Using multiple functional approaches, we show that the Kit tyrosine kinase receptor, expressed in MCCs, and its ligand Scf, expressed in outer-layer cells, are both required for regular MCC distribution. While Scf behaves as a potent adhesive cue for MCCs, Kit expression is sufficient to confer order to a disordered heterologous cell population. Our work reveals how a single signalling system can implement self-organised large-scale patterning. Highlights- Immature multiciliated cells transit from a disordered to an ordered pattern - The transition is a self-organising process based on repulsive and affinity movements - ARP2/3-dependent actin remodelling is required for pattern emergence - The SCF/KIT pathway promotes both repulsion and affinity movements eTOC blurbIn developing Xenopus epidermis, immature multiciliated cells (MCCs), initially chaotically distributed within an inner layer, emerge in an orderly pattern among cells of the outer layer. This process involves MCC mutual repulsion and affinity towards outer-layer intercellular junctions. The SCF/KIT signalling pathway promotes both properties to allow regular MCC distribution.

developmental biology↗

bioRxiv2019

Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability

Tissue remodeling during embryogenesis is driven by the apical contractility of the epithelial cell cortex. This behavior arises notably from Rho1/Rok induced transient accumulation of non-muscle myosin II (MyoII pulses) pulling on actin filaments (F-Actin) of the medio-apical cortex. While recent studies begin to highlight the mechanisms governing the emergence of Rho1/Rok/MyoII pulsatility in different organisms, little is known about how the F-Actin organization influences this process. Focusing on Drosophila ectodermal cells during germband extension and amnioserosa cells during dorsal closure, we show that the medio-apical actomyosin cortex consists of two entangled F-Actin subpopulations. One exhibits pulsatile dynamics of actin polymerization in a Rho1 dependent manner. The other forms a persistent and homogeneous network independent of Rho1. We identify the Frl/Fmnl formin as a critical nucleator of the persistent network since modulating its level, in mutants or by overexpression, decreases or increases the network density. Absence of this network yields sparse connectivity affecting the homogeneous force transmission to the cell boundaries. This reduces the propagation range of contractile forces and results in tissue scale morphogenetic defects. Our work sheds new lights on how the F-Actin cortex offers multiple levels of regulation to affect epithelial cells dynamics.

developmental biology↗

bioRxiv2018

Force inference predicts local and tissue-scale stress patterns in epithelia

Morphogenesis relies on the active generation of forces, and the transmission of these forces to surrounding cells and tissues. Hence measuring forces directly in developing embryos is an essential task to study the mechanics of development. Among the experimental techniques that have emerged to measure forces in epithelial tissues, force inference is particularly appealing. Indeed it only requires a snapshot of the tissue, as it relies on the topology and geometry of cell contacts, assuming that forces are balanced at each vertex. However, establishing force inference as a reliable technique requires thorough validation in multiple conditions. Here we performed systematic comparisons of force inference with laser ablation experiments in three distinct Drosophila epithelia. We show that force inference accurately predicts single junction tensions, tension patterns in stereotyped groups of cells, and tissue-scale stress patterns, in wild type and mutant conditions. We emphasize its ability to capture the distribution of forces at different scales from a single image, which gives it a critical advantage over perturbative techniques such as laser ablation. Our results demonstrate that force inference is a reliable and efficient method to quantify the mechanics of epithelial tissues during morphogenesis.

biophysics↗

bioRxiv2018

Cooption of antagonistic RNA-binding proteins establishes cell hierarchy in Drosophila neuro-developmental tumors

The mechanisms that govern the hierarchical organization of tumors are still poorly understood, especially in highly heterogeneous neural cancers. Previously, we had shown that aggressive neural tumors can be induced upon dedifferentiation of susceptible intermediate progenitors produced during early development (Narbonne-Reveau et al., 2016). Using clonal analysis, stochastic modelling and single-cell transcriptomics, we now find that such tumors rapidly become heterogeneous, containing progenitors with different proliferative potentials. We demonstrate that tumor heterogeneity emerges from the deregulated transition between two antagonistic RNA-binding proteins, Imp and Syncrip, that switch neural progenitors from a default self-renewing to a differentiation-prone state during development. Consequently, aberrant maintenance of Imp confers a cancer stem cell-like identity as Imp+ progenitors sustain tumor growth while being able to continuously generate Syncrip+ progenitors. The latter exhibit limited self-renewal likely due to Syncrip-mediated metabolic exhaustion. This study provides an example of how a subverted developmental transition establishes a hierarchical tumor.

developmental biology↗

bioRxiv2017

Viscoelastic dissipation stabilizes cell shape changes during tissue morphogenesis

Tissue morphogenesis relies on the production of active cellular forces. Understanding how such forces are mechanically converted into cell shape changes is essential to our understanding of morphogenesis. Here we use Myosin II pulsatile activity during Drosophila embryogenesis to study how transient forces generate irreversible cell shape changes. Analyzing the dynamics of junction shortening and elongation resulting from Myosin II pulses, we find that long pulses yield less reversible deformations, typically a signature of dissipative mechanics. This is consistent with a simple viscoelastic description, which we use to model individual shortening and elongation events. The model predicts that dissipation typically occurs on the minute timescale, a timescale commensurate with that of force generation by Myosin II pulses. We test this estimate by applying time-controlled forces on junctions with optical tweezers. Our results argue that active junctional deformation is stabilized by dissipation. Hence, tissue morphogenesis requires coordination between force generation and dissipation.

developmental biology↗