Biology subjects

Dupuis, C.

Publications and source records attributed to Dupuis, C..

8 recordsLinked to original sources

bioRxiv2026

Scaffold-Free Acoustic Levitation Platforms Enable Scalable Culture of Neuronal Spheroids and Assembly of Layered Cortico - Striatal Assembloids

Engineering three-dimensional neuronal tissues with defined architecture and functional connectivity remains a critical challenge for applications in disease modeling, drug discovery, and regenerative medicine. Recently, a variety of fabrication methods have arisen, such as bioprinting or manual assembly of organoids, but often struggle with scalability, reproducibility, or maintaining cell viability. Here, two scaffold-free acoustic levitation bioreactors are introduced: one optimized for the culture of uniform neuronal spheroids, and another designed for the structuration of assembloids composed of distinct neuronal identities. Using acoustic standing waves, these platforms enable the contactless manipulation of cells and aggregates, facilitating the formation of highly viable functionally mature spheroids. This study shows that both striatal and cortical cell aggregates formed in acoustic levitation self-organize into spheroids within 24 hours and remain viable up to 10 days under these particular culture conditions without medium renewal. These neuro-spheroids demonstrate healthy development with increased growth and typical terminal differentiation and synaptic maturation. Moreover, concentric cortico-striatal assembloids were successfully structured and cultivated using optimized acoustofluidic chips. Offering versatile and scalable tools for engineering complex neuronal networks, acoustic levitation reveals itself as an innovative approach to 3D neuronal tissue modeling, with broad implications for bioengineering, regenerative medicine and fundamental neuroscience research.

bioengineering↗

bioRxiv2025

Immune Cells Infiltration of Patient Derived Glioblastoma Cells spheroids in Acoustic Levitation in Bulk Acoustic Wave devices

We describe an acoustofluidic device that allows scaffold-free structuration and culture of multi-cellular tumoroids composed of patient-derived glioblastoma cells only or in combination with non-cancerous cell. A PDMS chip of controlled height was created to allow acoustic levitation of cells using a 2 MHz transducer held on top of the chip. Cells are introduced into the chip through a dedicated inlet upstream of the resonant cavity. The specific design of the cavity together with the acoustic field allow the formation of tumoroids of cells in a precise and controlled manner within the levitation chamber. The acoustic and fluidic environment of the device was determined through experiments confronted with numerical simulations. The control of the flow within the chip was optimized to allow long-term culture of tumoroids and injection of cell culture media without disturbing the tumoroids in levitation. The tumoroids can be also structured, with sequential injections of the different cell types. Using microglia, we show that the acoustofluidic device allows the formation and culture in acoustic levitation of tumoroids mixing cancer cells with other cells populating the tumor as well as immune cell infiltration within the tumoroids. These results demonstrate the suitability of acoustofluidic levitation as an original 3D culture method adapted to the exploration of cancer growth at multiple levels.

bioengineering↗

bioRxiv2024

Shared genetic architecture links energy metabolism, behavior and starvation resistance along a power-endurance axis

Shared developmental, physiological and molecular mechanisms can generate strong genetic covariances across suites of traits, constraining genetic variability and evolvability to certain axes in multivariate trait space ("variational modules" or "syndromes"). Such trait suites will not only respond jointly to selection; they will also covary across populations that diverged from one another by genetic drift. We report evidence for such a genetically correlated trait suite in Drosophila melanogaster. It links high expression of glycolysis and TCA cycle genes, high abundance of mitochondria and high spontaneous locomotor activity with low degree of adiposity, and low endurance and early death under starvation. This "power-endurance" axis is also aligned with abundance of certain metabolites, notably low trehalose (blood sugar) and high levels of some amino acids and their derivatives, including creatine, a compound known to facilitate energy production in muscles. Our evidence comes from six replicate "Selected" populations adapted to a nutrient-poor larval diet regime during 250 generations of experimental evolution and six "Control" populations evolved in parallel on a standard diet regime. We found that, within each of these experimental evolutionary regime, the above traits strongly covaried along the power-endurance axis across replicate populations which diversified by drift, indicating a shared genetic architecture. The two evolutionary regimes also drove divergence along this axis, with Selected populations on average displaced towards the "power" direction compared to Controls. Aspects of this "power-endurance" axis resemble the "pace of life" syndrome and the "thrifty phenotype"; it may have evolved as part of a coordinated organismal response to nutritional conditions.

evolutionary biology↗

bioRxiv2024

Microgravity stimulates network activity of 3D neuronal spheroids in an acoustic trap

Among biological models, cell culture constitutes an important paradigm that allows rapid examination of cell phenotype and behavior. While cell cultures are classically grown on a 2D substrate, the recent development of organoid technologies represents a paradigmatic shift in biological experimentation as they pave the way for the reconstruction of minimalist organs in 3D. Manipulating these 3D cell assemblies represents a considerable challenge. While there is growing interest in studying the behavior of cells and organs in the space environment, manipulating 3D cultures in microgravity remains a challenge. But with cellular research underway aboard the International Space Station (ISS), optimizing techniques for handling 3D cellular assemblies is essential. Here, in order to cultivate 3D models of spheroids in microgravity, we developed and used an acoustic bioreactor to trap levitating cellular organoids in a liquid cell culture medium. Indeed, in a Bulk Acoustic Wave (BAW) resonator, spherical objects, such as cells, can be maintained in an equilibrium position, inside a resonant cavity, away from the walls. In the acoustic levitation plane, gravity is counterbalanced by the acoustic radiation force (ARF) making it possible to maintain an object even in weightlessness. A dedicated setup was designed and built to perform live calcium imaging during parabolic flights. During a parabolic flight campaign, we were able to monitor the calcium activity of 3D neural networks trapped in an acoustic field during changes in gravity during different parabolas. Our results clearly indicate a change in calcium activity associated with variations in gravity.

biophysics↗

bioRxiv2022

Evolution under juvenile malnutrition impacts adult metabolism and fitness

Juvenile undernutrition has lasting effects on adult metabolism of the affected individuals, but it is unclear how adult physiology is shaped over evolutionary time by natural selection driven by juvenile undernutrition. We combined RNAseq, targeted metabolomics and genomics to study the consequences of evolution under juvenile undernutrition for metabolism of reproductively active adult females of Drosophila melanogaster. Compared to Control populations maintained on standard diet, Selected populations maintained for over 230 generations on a nutrient-poor larval diet evolved major changes in adult gene expression and metabolite abundance, in particular affecting amino-acid and purine metabolism. The evolved differences in adult gene expression and metabolite abundance between Selected and Control populations were positively correlated with the corresponding differences previously reported for Selected versus Control larvae. This implies that genetic variants affect both stages similarly. Even when well fed, the metabolic profile of Selected flies resembled that of flies subject to starvation. Finally, Selected flies had lower reproductive output than Controls even when both were raised under the conditions under which the Selected populations evolved. These results imply that evolutionary adaptation to juvenile undernutrition has large pleiotropic consequences for adult metabolism, and that they are costly rather than adaptive for adult fitness. Thus, juvenile and adult metabolism do not appear to evolve independently from each other even in a holometabolous species where the two life stages are separated by a complete metamorphosis.

evolutionary biology↗

bioRxiv2021

Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behaviour and associated brain modulations is challenging. Here we tackled this question implementing a prism adaptation training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N=45) underwent VRPA (with a spatial shift either to the left/right side, or with no shift), and performed fMRI sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting state and free viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between large-scale cortical networks - namely attentional and default mode/fronto-parietal networks - only for adaptation groups. Additionally, VRPA was found to bias visual representations of naturalistic videos, as following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA induced after-effect measured in behavioural tests. This study demonstrates that a brief VRPA exposure is able to change large-scale cortical connectivity and correspondingly bias the representation of naturalistic sensory inputs. Significance statementIn the current work, we tested how a brief sensorimotor experience changes subsequent brain activity and connectivity. Using virtual reality (VR) as a tool for sensorimotor training opens a window for creating otherwise impossible sensory experiences and sensorimotor interactions. Specifically, we studied how VR adaptation training in ecological conditions modulates spontaneous functional connectivity and brain representation of naturalistic real-life-like stimuli. Previous adaptation studies used artificial, lab-designed setups both during adaptation and while measuring subsequent aftereffects. Testing brain response while observing naturalistic stimuli and in resting state allowed us to stay as close as possible to naturalistic real-life-like conditions, not confounded by performance during a task. The current work demonstrates how rapid changes in free-flowing brain activity and connectivity occur following short-term VR visuomotor adaptation training in healthy individuals. Moreover, we found a link between sensory responses to naturalistic stimuli and adaptation-induced behavioural aftereffect, thus demonstrating a common source of training-induced spatial recalibration, which affects both behaviour and brain representations of naturalistic stimuli. These findings might have meaningful implications both for understanding the mechanisms underlying visuomotor plasticity in healthy individuals and for using VR adaptation training as a tool for rehabilitating brain-damaged patients suffering from deficits in spatial representation.

neuroscience↗

bioRxiv2020

The genomic architecture of adaptation to larval malnutrition points to a trade-off with adult starvation resistance in Drosophila

Periods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. We studied the genomic signature of adaptation to chronic juvenile malnutrition in six populations of Drosophila melanogaster evolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving >3,000 candidate SNPs forming >100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajimas D, suggests that the poor diet results in balancing selection on some genomic regions. Our candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in our study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress.

evolutionary biology↗

bioRxiv2018

Dual RNA-seq reveals large-scale non-conserved genotype x genotype specific genetic reprograming and molecular crosstalk in the mycorrhizal symbiosis

Arbuscular mycorrhizal fungi (AMF) impact plant growth and are a major driver of plant diversity and productivity. We quantified the contribution of intra-specific genetic variability in cassava (Manihot esculenta) and Rhizophagus irregularis to gene reprogramming in symbioses using dual RNA-sequencing. A large number of cassava genes exhibited altered transcriptional responses to the fungus but transcription of most of these plant genes (72%) responded in a different direction or magnitude depending on the plant genotype. Two AMF isolates displayed large differences in their transcription, but the direction and magnitude of the transcriptional responses for a large number of these genes was also strongly influenced by the genotype of the plant host. This indicates that unlike the highly conserved plant genes necessary for the symbiosis establishment, plant and fungal gene transcriptional responses are not conserved and are greatly influenced by plant and fungal genetic differences, even at the within-species level. The transcriptional variability detected allowed us to identify an extensive gene network showing the interplay in plant-fungal reprogramming in the symbiosis. Key genes illustrated that the two organisms jointly program their cytoskeleton organisation during growth of the fungus inside roots. Our study reveals that plant and fungal genetic variation plays a strong role in shaping the genetic reprograming in response to symbiosis, indicating considerable genotype x genotype interactions in the mycorrhizal symbiosis. Such variation needs to be considered in order to understand the molecular mechanisms between AMF and their plant hosts in natural communities.

plant biology↗