Biology subjects

Aymard, P.

Publications and source records attributed to Aymard, P..

3 recordsLinked to original sources

bioRxiv2024

A single-cell atlas of transcriptome changes in the intestinal epithelium at the suckling-to-weaning transition

The suckling-to-weaning dietary transition is a key step in mammalian intestinal development. However, the relative contributions of genetically wired and nutritional factors in this maturation process remain to be elucidated. Moreover, the cellular diversity of the intestinal epithelium has been overlooked in this context. The aim of our study was to identify the transcriptome changes induced in each cell type of the intestinal epithelium at the onset of solid food ingestion. We compared the single-cell transcriptome of epithelial cells isolated from the caecum of age-matched littermate suckling rabbits ingesting or not solid food. Our dataset provides the first single-cell atlas of the rabbit intestinal epithelium and highlights the interest of the rabbit as a model for studying BEST4+ epithelial cells, which are absent in mice. Solid food ingestion induced extensive transcriptome changes in each epithelial cell type, with the most pronounced changes noted in absorptive and BEST4+ cells. Some of the effects of solid food introduction were common to most epithelial cell types, such as the upregulation of ALDH1A1, which encodes for a vitamin A processing enzyme. Solid food ingestion remodeled epithelial defenses systems, as observed by the increased expression of interferon-stimulated genes in mature absorptive and BEST4+ cells. Solid food also upregulated the gene expression of the immunoglobulin transporter PIGR, specifically in cells located at the base of epithelial crypts and in goblet cells. In addition, solid food triggered epithelial differentiation, which was associated with modification of the expression of genes involved in handling of amino acids, lipids and bile acids, as well as changes in hormone expression by enteroendocrine cells. These cell type-specific transcriptome modifications induced by solid food ingestion coincided with changes in microbiota composition and metabolic activity, which may contribute to epithelial maturation. Overall, our work provides a single-cell atlas of the transcriptome changes induced in the intestinal epithelium at the suckling-to-weaning transition.

physiology↗

bioRxiv2024

Unveiling the Functional Connectivity of Astrocytic Networks with AstroNet, a Graph Reconstruction Algorithm Coupled to Image Processing

Astrocytes form extended intercellular networks, displaying complex calcium activity. However, the specific organization of these astrocytic networks and the precise extent of their functional connectivity in different brain areas remain unexplored. To unveil the functional architecture of astrocytic networks, we developed, using a data-driven methodology, a novel algorithm called AstroNet that uses two-photon calcium imaging to map temporal correlations in activation events among neighboring astro-cytes. Our approach involves reconstructing functional astrocytic networks by organizing individual astrocyte activation events chronologically. This chronological order creates activity paths that enable the extraction of local astrocyte functional correlations. Ultimately, by tallying the occurrences of direct co-activations between pairs of cells along these pathways, we construct a graph that mirrors the underlying astrocyte functional network. By applying this method to two distinct brain regions (CA1 hippocampus and motor cortex), we identified notable differences in local network organizations in sub-regions of around 20-40 astrocytes. Specifically, the cortex exhibited a lower connectivity, while astrocytes in the hippocampus displayed stronger connections. Moreover, we found that in both regions, astrocytic networks consist of smaller, tightly connected sub-networks embedded within a larger, more loosely connected one. Altogether, our innovative method enables the identification of activation paths among astrocytes, facilitates the characterization of local network functional connectivity, and quantifies distinct connectivity patterns among astrocytes from different brain regions. This approach sheds light on the heterogeneous functional organization of astrocytic networks within the brain, pointing to region-specific astrocyte connectivity.

neuroscience↗

bioRxiv2021

A genome-wide epistatic network underlies the molecular architecture of continuous color variation of body extremities: a rabbit model

Deciphering the molecular architecture of coat coloration for a better understanding of the biological mechanisms underlying pigmentation still remains a challenge. We took advantage of a rabbit French experimental population in which both a pattern and a gradient of coloration from white to brown segregated within the himalayan phenotype. The whole experimental design was genotyped using the high density Affymetrix(R) AxiomOrcun SNP Array and phenotyped into 6 different groups ordered from the lighter to the darker. Genome-wide association analyses pinpointed an oligogenic determinism, under recessive and additive inheritance, involving genes already known in melanogenesis (ASIP, KIT, MC1R, TYR), and likely processed pseudogenes linked to ribosomal function, RPS20 and RPS14. We also identified (i) gene-gene interactions through ASIP:MC1R affecting light cream/beige phenotypes while KIT:RPS responsible of dark chocolate/brown colors and (ii) a genome-wide epistatic network involving several others coloration genes such as POT1 or HPS5. Finally, we determined the recessive inheritance of the English spotting phenotype likely involving a copy number variation affecting at least the end of the coding sequence of the KIT gene. Our analyses of coloration as a continuous trait allowed us to go beyond much of the established knowledge through the detection of additional genes and gene-gene interactions that may contribute to the molecular architecture of the coloration phenotype. Moreover, the characterization of a network including genes that contribute to melanogenesis and pigmentation, two processes affected in various human disorders, shows the potential interest of our rabbit model for transversal studies.

genetics↗