Biology subjects

Auger, S.

Publications and source records attributed to Auger, S..

3 recordsLinked to original sources

bioRxiv2024

Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors

Protein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the synthesis of the alkyne-containing isoprenoid analogue C15AlkOPP are reported to improve synthetic efficiency. Next, metabolic labeling with C15AlkOPP was optimized to obtain useful levels of metabolic incorporation of the probe in several types of primary cells. Those conditions were then used to study the prenylomes of motor neurons (ES-MNs), astrocytes (ES-As), and their embryonic stem cell progenitors (ESCs), which allowed for the identification of 54 prenylated proteins from ESCs, 50 from ES-MNs and 84 from ES-As, representing all types of prenylation. Bioinformatic analysis revealed specific enriched pathways, including nervous system development, chemokine signaling, Rho GTPase signaling, and adhesion. Hierarchical clustering showed that most enriched pathways in all three cell types are related to GTPase activity and vesicular transport. In contrast, STRING analysis showed significant interactions in two populations that appear to be cell type dependent. The data provided herein demonstrates that robust incorporation of C15AlkOPP can be obtained in ES-MNs and related primary cells purified via magnetic-activated cell sorting allowing the identification and quantification of numerous prenylated proteins. These results suggest that metabolic labeling with C15AlkOPP should be an effective approach for investigating the role of prenylated proteins in primary cells in both normal cells and disease pathologies, including ALS. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/583211v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@193cfe1org.highwire.dtl.DTLVardef@134edccorg.highwire.dtl.DTLVardef@1e81deforg.highwire.dtl.DTLVardef@56406_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis (Dammann, O. and Leviton, A., Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res, 2014. 75(3): p. 376-80). In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery (Luca, A.,et al., Birth trauma in preterm spontaneous vaginal and cesarean section deliveries: A 10-years retrospective study. PloS one,2022, 17(10), e0275726.) We have developed and characterized a mouse model based on intraperitoneal injections of IL-1{beta} between postnatal days one and five to reproduce perinatal systemic inflammation (Favrais, G.,et al., Systemic inflammation disrupts the developmental program of white matter. Ann Neurol,2011. 70(4): p. 550-65). This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1{beta} on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders. Significance StatementIn a well-established mouse model of the encephalopathy of prematurity, we observed that C-section exacerbates the deleterious effects of neonatal systemic inflammation (intraperitoneal injections of IL-1{beta} between postnatal days one and five) on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced brain functional connectivity. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.

neuroscience↗

bioRxiv2022

Gene co-expression network analysis of the human gut commensal bacterium Faecalibacterium prausnitzii based on WGCNA in R-Shiny

Faecalibacterium prausnitzii is abundant in the healthy human intestinal microbiota, and the absence or scarcity of this bacterium has been linked with inflammatory diseases and metabolic disorders. F. prausnitzii thus shows promise as a next-generation probiotic for use in restoring the balance of the gut microbial flora and, due to its strong anti-inflammatory properties, for the treatment of certain pathological conditions. However, very little information is available about gene function and regulation in this species. Here, we utilized a systems biology approach - weighted gene co-expression network analysis (WGCNA) - to analyze gene expression in three publicly available RNAseq datasets from F. prausnitzii strain A2-165, all obtained in different laboratory conditions. The co-expression network was then subdivided into 24 co-expression gene modules. A subsequent enrichment analysis revealed that these modules are associated with different kinds of biological processes, such as arginine, histidine, cobalamin, or fatty acid metabolism as well as bacteriophage function, molecular chaperones, stress response, or SOS response. Some genes appeared to be associated with mechanisms of protection against oxidative stress and could be essential for F. prausnitziis adaptation and survival under anaerobic laboratory conditions. Hub and bottleneck genes were identified by analyses of intramodular connectivity and betweenness, respectively; this highlighted the high connectivity of genes located on mobile genetic elements, which could promote the genetic evolution of F. prausnitzii within its ecological niche. This study provides the first exploration of the complex regulatory networks in F. prausnitzii, and all of the "omics" data are available online for exploration through a graphical interface at https://feaprau.omics.ovh/.

microbiology↗