Biology subjects

Clement, F.

Publications and source records attributed to Clement, F..

4 recordsLinked to original sources

bioRxiv2026

Human decellularized extracellular matrix from adipose tissue is a permissive microenvironment for pancreatic organoids generation

In vitro reconstruction of human tissue microenvironments that integrate native biochemical and biomechanical cues is essential for disease modelling, regenerative medicine, and personalized therapeutic approaches. However, most currently available engineered matrices fail to recapitulate the complexity and tissue specificity of the human extracellular matrix (ECM). To address this limitation, we developed a novel hydrogel derived from decellularized human adipose tissue (atdECM) designed to support three-dimensional culture of human cells. The decellularization and delipidation processes were first validated, and the biochemical composition and biomechanical properties of atdECM were comprehensively characterized. Human pancreatic organoids were then cultured within atdECM hydrogel, and their structural organization and transcriptional profiles were analyzed and compared with those obtained in Matrigel, the current gold-standard matrix for organoid culture. Proteomic and cytokine analyses demonstrated efficient decellularization while preserving collagen-rich ECM architecture and a diverse repertoire of soluble bioactive factors. AtdECM exhibited physiological stiffness and retained tissue-specific extracellular cues. Pancreatic organoids cultured in atdECM displayed morphological similarities with those grown in Matrigel but exhibited transcriptional profiles more consistent with physiological epithelial homeostasis, with reduced activation of inflammatory and stress-related pathways. Altogether, these findings indicate that atdECM provides a human-derived, tissue-relevant, and permissive microenvironment for human organoid generation. This platform represents a promising alternative to Matrigel for studying human tissue biology and for developing physiologically relevant in vitro models.

bioengineering↗

bioRxiv2024

Oxytocin and shared intentionality drive variation in cooperation in children

While humans cooperate with unrelated individuals to an extent that far outstrips any other species, we also display extreme variation in decisions about whether to cooperate or not. A diversity of cognitive, affective, social, and physiological mechanisms interact to shape these decisions. For example, group membership, shared intentionality talk (i.e. talk about shared goals), and natural initial oxytocin levels affect cooperation in adults in an optimal foraging paradigm that is loosely modelled on the iterated prisoners dilemma. In this egg hunt, shared intentionality talk was key to achieve cooperation, and it occurred more between participants who shared the same group membership and had higher initial oxytocin levels. Such complex interactions raise the question of the age at which humans develop the necessary mechanisms to cooperate effectively in the egg hunt game. Here, we tested children in secondary school aged between 10 and 14 years. We found that, as for adults, shared intentionality talk was crucial for successful cooperation. Furthermore, initial oxytocin levels affected cooperation through shared intentionality talk. In contrast, group membership did not affect behaviour. Finally, pre- and post-experiment oxytocin levels showed various interactions with group membership and gender. Thus, childrens performance was relatively similar to adults while showing some differences with respect to underlying mechanisms. Our study is a rare contribution to further our understanding of the role of oxytocin in early adolescent social behaviour.

developmental biology↗

bioRxiv2022

Method for quantifying the metabolic boundary fluxes of cell cultures in large cohorts by high resolution hydrophilic liquid chromatography mass spectrometry

Metabolomics is a mainstream approach for investigating the metabolic underpinnings of complex biological phenomena and is increasingly being applied to large scale studies involving hundreds or thousands of samples. Although metabolomics methods are robust in smaller scale studies, they can be challenging to apply in larger cohorts due to the inherent variability of liquid chromatography mass spectrometry (LC-MS). Much of this difficulty results from the time-dependent changes in the LC-MS system, which affects both the qualitative and quantitative performance of the instrument. Herein, we introduce an analytical strategy for addressing this problem in large-scale microbial studies. Our approach quantifies microbial boundary fluxes using two zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) columns that are plumbed to enable offline column equilibration. Using this strategy, we show that over 360 common metabolites can be resolved in 4.5 minutes per sample and that metabolites can be quantified with a median coefficient of variation of 0.127 across 1,100 technical replicates. We illustrate the utility of this strategy via an analysis of 960 strains of Staphylococcus aureus isolated from blood stream infections. These data capture the diversity of metabolic phenotypes observed in clinical isolates and provide an example of how large-scale investigations can leverage our novel analytical strategy.

biochemistry↗

bioRxiv2021

Tuning the immunostimulation properties of cationic lipid nanocarriers for nucleic acid delivery

Nonviral systems, such as lipid nanoparticles, have emerged as reliable methods to enable nucleic acid intracellular delivery. The use of cationic lipids in various formulations of lipid nanoparticles enables the formation of complexes with nucleic acid cargo and facilitates their uptake by target cells. However, due to their small size and highly charged nature, these nanocarrier systems can interact in vivo with antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages. As this might prove to be a safety concern for developing therapies based on lipid nanocarriers, we sought to understand how they could affect the physiology of APCs. In the present study, we investigate the cellular and metabolic response of primary macrophages or DCs exposed to the neutral or cationic variant of the same lipid nanoparticle formulation. We demonstrate that macrophages are the cells affected most significantly and that the cationic nanocarrier has a substantial impact on their physiology, depending on the positive surface charge. Our study provides a first model explaining the impact of charged lipid materials on immune cells and demonstrates that the primary adverse effects observed can be prevented by fine-tuning the load of nucleic acid cargo. Finally, we bring rationale to calibrate the nucleic acid load of cationic lipid nanocarriers depending on whether immunostimulation is desirable with the intended therapeutic application, for instance, gene delivery or messenger RNA vaccines.

immunology↗