Biology subjects

Duret, C.

Publications and source records attributed to Duret, C..

4 recordsLinked to original sources

bioRxiv2026

Declining muscle hyperplasia in juvenile trout is driven by rapid limitation of muscle stem cell capacity and niche functionality

Unlike mammals and birds, where new muscle fiber formation (hyperplasia) ceases around birth, large and fast-growing fish such as rainbow trout undergo a spectacular post-hatching surge of hyperplasia, followed by a considerably delayed hyperplasia decline. This study investigated the roles of the satellite cells (SCs) and their niche in this decline by determining the number and the myogenic capacity of the muscle progenitors as well as the functionality of their direct tissue environment. Histological analysis revealed a significant decrease in hyperplasia (fibers <25 {micro}m) and SC numbers (Pax7+) between 10 g and 500 g trout. Transplantation experiments using muscle-derived cells (MDCs) from mlc2-GFP transgenic trout (10 g to 2 kg donors into 10 g to 2 kg recipients) demonstrated a marked decline in both intrinsic myogenic capacity and niche functionality as trout grow from 10 g to 500 g. Detailed analyses of GFP+ fibers produced after transplantation showed an enrichment of small-diameter GFP+ fibers in 10 g but not 100 g trout recipient muscles, showing a rapid impairment in niche ability to support hyperplasia. In addition, transplantation of MDCs from trout of different ages but the same weight, showed that increasing trout weight, but not aging, is associated with an impairment of the myogenic capacity of progenitors and their niche. Overall, these findings show that the muscle hyperplasia decline in trout is primarily driven by early impairment of the SC niche, followed by a reduction in their myogenic capacity and number, with weight gain playing a more critical role than aging.

cell biology↗

bioRxiv2023

2D cell culture on soft hydrogel drives an endoplasmic reticulum stress-dependent S quiescence underlying molecular traits of pulmonary basal cells

Cell culture on soft matrix, either in 2D and 3D, preserves the characteristics of progenitors. However, the mechanism by which the mechanical microenvironment determines progenitor phenotype, and its relevance to human biology, remains poorly described. Here we designed multi-well hydrogel plates with a high degree of physico-chemical uniformity to reliably address the molecular mechanism underlying cell state modification driven by physiological stiffness. Cell cycle, differentiation and metabolic activity could be studied in parallel assays, showing that the soft environment promotes an atypical S-phase quiescence and prevents cell drift, while preserving the differentiation capacities of human bronchoepithelial cells. These softness-sensitive responses are driven by defects in proteostasis and enhanced basal endoplasmic reticulum stress. The analysis of available single cell data of the human lung also showed that this non-conventional state coming from the soft extracellular environment is indeed consistent with molecular feature of pulmonary basal cells. Overall, this study demonstrates that mechanical mimicry in 2D culture supports allows to maintain progenitor cells in a state of high physiological relevance for characterizing novel molecular events that govern progenitor biology in human tissues.

cell biology↗

bioRxiv2023

Targeting the cell and non-cell autonomous regulation of 47S synthesis by GCN2 in colon cancer.

Nutrient availability is a key determinant of tumor cell behavior. While nutrient-rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor GCN2 represses the expression of the precursor of ribosomal RNA, 47S, under metabolic stress. We show that blockade of GCN2 triggers cell death by an irremediable nucleolar stress and subsequent TP53-mediated apoptosis in patient-derived models of colon adenocarcinoma (COAD). In nutrient-rich conditions, GCN2 activity supports cell proliferation through the transcription stimulation of 47S rRNA, independently of the canonical ISR axis. However, impairment of GCN2 activity prevents nuclear translocation of the methionyl tRNA synthetase (MetRS) underlying the generation of a nucleolar stress, mTORC1 inhibition and autophagy induction. Inhibition of the GCN2-MetRS axis drastically improves the cytotoxicity of RNA pol I inhibitors, including the first-line chemotherapy oxaliplatin, on patient-derived COAD tumoroids. Our data thus reveal that GCN2 differentially controls the ribosome biogenesis according the nutritional context. Furthermore, pharmacological co-inhibition of the two GCN2 branches and the RNA pol I activity may represent a valuable strategy for elimination of proliferative and metabolically-stressed COAD cell.

cancer biology↗

bioRxiv2017

Anatomical Predictors Of Recovery From Visual Neglect After Prism Adaptation Therapy

Visual neglect is a frequent and disabling consequence of right hemisphere damage. Previous work demonstrated a probable role of posterior callosal dysfunction in the chronic persistence of neglect signs. Prism adaptation is a non-invasive and convenient technique to rehabilitate chronic visual neglect, but it is not effective in all patients. Here we aimed to assess the hypothesis that prism adaptation improves left neglect by facilitating compensation through the contribution of the left, undamaged hemisphere. We assessed the relationship between prism adaptation effects, cortical thickness and white matter integrity in a group of 14 patients with unilateral right-hemisphere strokes and chronic visual neglect. Results showed that patients who benefitted from prism adaptation had thicker cortex in temporo-parietal, prefrontal and cingulate areas of the left, undamaged hemisphere. Additionally, these patients had a higher fractional anisotropy value in the body and genu of the corpus callosum. Results from normal controls show that these callosal regions connect temporo-parietal, sensorimotor and prefrontal areas. Finally, shorter time intervals from the stroke tended to improve patients response to prism adaptation. We concluded that prism adaptation may improve left visual neglect by promoting the contribution of the left hemisphere to neglect compensation. These results support current hypotheses on the role of the healthy hemisphere in the compensation for stroke-induced, chronic neuropsychological deficits, and suggest that prism adaptation can foster this role by exploiting sensorimotor/prefrontal circuits, especially when applied at early stages post-stroke.

neuroscience↗