Biology subjects

Faure, S.

Publications and source records attributed to Faure, S..

9 recordsLinked to original sources

bioRxiv2025

The Paraphyletic Origins of Genetic Resistance to Cabbage Stem Flea Beetle in Brassica oleracea

The cabbage stem flea beetle (CSFB) poses a growing threat to winter Brassica crops in Europe, yet the genetic basis of resistance remains poorly understood. To clarify the genetic architecture and evolutionary origins of resistance to CSFB adult feeding, we conducted a genome-wide association study (GWAS) by combining high-throughput pool-sequencing and a large-scale non-choice feeding assay on 113 Brassica oleracea accessions from wild (or feral) populations and major domesticated morphotypes. We demonstrate that resistance displays moderate heritability with a predominantly polygenic basis, revealing strong phenotypic divergence among morphotypes: B. oleracea var. capitata was generally susceptible, whereas var. botrytis and wild populations showed markedly higher resistance. Despite this polygenic background, we identified a major-effect candidate QTL on chromosome C01 with strong enrichment of resistance alleles in wild populations and susceptible alleles in var. capitata. Genome-wide F-statistics and heterozygosity scans revealed a recent selective sweep at this locus in wild lineages. Considering current evidence for the feral origin of contemporary "wild" populations, our results suggest that resistance evolved after domestication and subsequent feralization, independently of resistance in var. botrytis. This paraphyletic distribution underlines the critical importance of integrating demographic history into quantitative genetic analyses of domesticated plant systems.

genetics↗

bioRxiv2025

Conserved 'late' effector genes from Leptosphaeria maculans inducing gene-for-gene quantitative resistance in Brassica napus semi-winter genotypes

Leptosphaeria maculans is a phytopathogenic fungus responsible for stem canker on Brassica napus. Its infectious cycle goes through an early phase of leaf infection and a late phase of colonization and infection of the stem. The disease is mainly controlled by plant genetic resistances targeting a limited set of early fungal effector genes overexpressed during leaf infection and located in dynamic repeat-rich genomic regions. Thus, these resistances can be rapidly overcome by the pathogen. To find new sources of resistance, we focused on late effector genes, expressed during stem infection and located in gene-rich regions. A previous study revealed a quantitative resistance in the stem partly relying on a gene-for-gene interaction with a late effector gene. In this study, we deciphered whether all late effector genes shared the same genomic and evolutionary characteristics and if they could be more stable than early effector genes, rendering the resistances they trigger more durable. In addition, as previous studies highlighted new criteria for selecting late effectors and suggested B. napus semi-winter genotypes as an interesting genetic pool for uncovering resistance sources, we selected six new late effector gene candidates and screened an enlarged panel of semi-winter genotypes. We revealed that early and late effector genes diverged for most of their genomic characteristics supplying for the hypothesis of late effector genes being more conserved. Moreover, we revealed new resistance sources to late effector genes, almost all belonging to the semi-winter genetic pool, validating their importance to uncover new resistance sources.

plant biology↗

bioRxiv2025

Breaking the redundancy: TAZ outperforms YAP1 in GIST progression

BackgroundGastrointestinal stromal tumors (GIST) are mainly caused by gain-of-function mutations in KIT or PDGFRA genes and are the most common neoplasms of the digestive tract. Imatinib (IM), a tyrosine kinase inhibitor (TKI) targeting these oncogenic drivers, has considerably improved patient outcomes, although resistance remains a major challenge. The transcriptional co-activators YAP1 and TAZ, downstream effectors of the Hippo pathway, have emerged as potential oncogenic drivers in various cancers, including GIST. However, their specific roles in KIT-dependent tumor development remain unclear. MethodsWe used WRAP5-based nanoparticles loaded with specifically designed siRNA to selectively silence YAP1 and/or TAZ proteins in KIT-dependent IM-sensitive GIST cell lines. This nucleic acid delivery system enabled efficient and specific knockdown without cytotoxicity. We assessed the impact on cell proliferation, migration, and gene expression, focusing on YAP1/TAZ targets CYR61 and CTGF. ResultsTAZ silencing resulted in a substantial reduction in GIST-T1 cell proliferation and migration, whereas YAP1 knockdown was comparatively limited. This finding was consistent with an increased TAZ expression in GIST patients, which was associated with shorter progression-free survival and an increased tendency for metastasis development. A slight additive effect was observed upon a combined YAP1/TAZ silencing in the migration assay, suggesting a more complex regulation between these two proteins. CYR61 and CTGF expressions were predominantly regulated by TAZ, though a stronger downregulation was observed upon dual knockdown in a subset of GIST cell lines with differential YAP1 and TAZ basal expression. Finally, CYR61 seemed to be more implicated in cell proliferation inhibition, which is further supported by the correlation between high CYR61 expression and poor prognosis in the GIST patients. ConclusionOur results highlight the central regulatory function of TAZ-CYR61 axis in oncogenic processes in KIT-dependent GIST, with a modest contribution from YAP1. Targeting TAZ, alone or in combination with YAP1, may represent a promising therapeutic approach, particularly in the context of tumor heterogeneity.

cancer biology↗

bioRxiv2025

Three-Dimensional-Mapping of Smooth Muscle Morphogenesis in the Vertebrate Gastrointestinal Tract

Gastrointestinal (GI) motility depends on smooth muscle contractions to propel contents through the digestive tract. GI muscle is organized into two perpendicular layers: the inner circular smooth muscle (CSM) and the outer longitudinal smooth muscle (LSM) layers. This organization is important for proper motility. Despite several investigations, GI smooth muscle development remains poorly understood due to several limitations. Previous studies mainly relied on SMA detection in tissue sections and focused on a single organ or developmental stage. They often overlooked key smooth muscle markers such as CALPONIN and {gamma}SMA and largely neglected the LSM layer. In this study, we combined confocal imaging of whole-mount three-dimensional-cleared embryonic chick guts with heatmap analysis to generate the first spatial atlas of smooth muscle development. We characterize the expression patterns of SMA, {gamma}SMA, and CALPONIN1, thereby mapping the dynamics of the formation and differentiation of CSM and LSM layers along the antero-posterior axis. This study provides a framework for future investigations into the regulatory mechanisms governing smooth muscle patterning and maturation along the GI tract.

developmental biology↗

bioRxiv2025

Multi-protein silencing using WRAP-based nanoparticles: a proof of concept

Cancer remains the leading cause of death, with chemotherapy, radiotherapy, and surgical resection being the primary treatment methods. However, chemotherapys side effects, surgical limitations, and drug resistance present significant challenges. Small interfering RNA (siRNA) has emerged as a promising tool in cancer therapy due to its ability to silence disease-related genes selectively. Recent advancements in non-viral delivery systems, particularly cell-penetrating peptides (CPPs), have enhanced the efficacy of siRNA delivery. The use of siRNA as a therapeutic tool in cancer treatment has been reported. However, silencing only one target protein has only minor effects on tumor cell proliferation as previously shown for WRAP-based nanoparticles targeting cyclin-dependent kinase 4 (CDK4) in human glioblastoma cells. Here, we designed a more sophisticated approach to enhance therapeutic efficacy, encapsulating multiple siRNAs targeting CDK4, cyclin D1 (CD1), and Mcl-1 proteins. The siRNA cocktail, delivered via WRAP5 nanoparticles, effectively silenced these targets and reduced cell proliferation in human glioblastoma cells. Furthermore, the nanoparticles also demonstrated potential therapeutic impact in gastrointestinal stromal tumors (GIST), a rare cancer characterized by its tendency to resist standard treatments. This study highlights the versatility of WRAP5 nanoparticles as a platform for personalized cancer therapy, suggesting that siRNA delivery systems may be tailored to specific cancer types for more effective treatment strategies.

cell biology↗

bioRxiv2024

Obesity induces phenotypic switching of gastric smooth muscle cells through the activation of the PPARD/PDK4/ANGPTL4 pathway

ObjectiveClinical research has identified stomach dysmotility as a common feature of obesity. However, the specific mechanisms driving gastric emptying dysfunction in patients with obesity remain largely unknown. In this study, we investigated potential mechanisms by focusing on the homeostasis of gastric smooth muscle, using tissue samples from both patient and mice, as well as human cell culture system. DesignTissue samples were collected from patients who underwent sleeve gastrectomy for obesity, as well as from control subjects with standard weight who were undergoing treatment for gastric or esophageal carcinoma. Stomach tissues were harvested from mice after 12 weeks on a High-Fat Diet (HFD). Differentiated human gastric smooth muscle cells (SMCs) were treated with lipids, siRNA-peptide-based nanoparticles and/or pharmaceutical compounds. All experimental conditions were analyzed for their effects on SMC differentiation using stage-specific smooth muscle markers. Additionally, lipidomic and RNA sequencing analyses were performed on human gastric SMC cultures. The findings were assessed in patients with obesity to evaluate their clinical relevance. ResultsThe smooth muscle layers in gastric tissue from both patients with obesity and mice fed on a HFD exhibited altered differentiation status. Treatment of differentiated human gastric SMCs with lipids phenocopies these alterations and is associated with increased expression of PDK4 and ANGPTL4. Inhibition of PDK4 or ANGPTL4 upregulation prevents these lipid-induced modifications. Mechanistically, lipid treatment activates PPARD, which regulates PDK4 and ANGPTL4 upregulation, leading to SMC dedifferentiation. Notably, PDK4 and ANGPTL4 levels correlate with immaturity and alteration of gastric smooth muscle in patients with obesity. ConclusionObesity triggers a phenotypic change in gastric SMCs, driven by the activation of the PPARD/PDK4/ANGPTL4 pathway. These mechanistic insights offer potential biomarkers for diagnosing stomach dysmotility in patients with obesity.

physiology↗

bioRxiv2022

High-Resolution Ultrasound and Speckle Tracking: a non-invasive approach to assess in vivo gastrointestinal motility during development

Gastrointestinal motor activity has been extensively studied in adults, conversely only few studies have investigated fetal motor skills. When the gastrointestinal tract starts to contract during the embryonic period and how this function evolves during development are not known. Here, we adapted a non-invasive high-resolution echography technique combined with speckle tracking analysis to examine the gastrointestinal tract motor activity dynamics during chick embryo development. We provided the first recordings of fetal gastrointestinal motility in living embryos. We found that although gastrointestinal contractions appear very early during development, they become synchronized only at the end of the fetal period. To validate this approach, we used various pharmacological inhibitors and BAPX1 gene overexpression in vivo. We found that the enteric nervous system determinates the onset of the synchronized contractions in the stomach. Moreover, alteration of smooth muscle fiber organization led to an impairment of this functional activity. Altogether, our findings show that non-invasive high-resolution echography and speckle tracking analysis allow visualizing and quantifying gastrointestinal motility during development and highlight the progressive acquisition of functional and coordinated gastrointestinal motility before birth.

developmental biology↗

bioRxiv2022

LIX1 controls digestive mesenchyme-derived cell fate decision by regulating cristae organization in mitochondria

Limb Expression 1 (LIX1) is a master regulator of digestive mesenchymal progenitor and GastroIntestinal Stromal Tumor (GIST) cell proliferation by controlling the expression of the Hippo effectors YAP1/TAZ and KIT. However, the underlying mechanisms of these LIX1-mediated regulations and tumor promotion remain to be elucidated. Here, we report that LIX1 is S-palmitoylated on cysteine 84 and localized in mitochondria. LIX1 knock-down affects the mitochondrial ultrastructure, resulting in decreased respiration and mitochondrial reactive oxygen species production. This is sufficient to downregulate YAP1/TAZ and reprogram KIT-positive GIST cells towards the smooth muscle cell lineage with reduced proliferative and invasive capacities. Mechanistically, LIX1 knock-down impairs the stability of the mitochondrial proteins PHB2 and OPA1 that are found in complexes with mitochondrial-specific phospholipids and are required for cristae organization. Supplementation with unsaturated fatty acids counteracts the effects of LIX1 knock-down on mitochondrial morphology and ultrastructure, restores YAP1/TAZ signaling, and consequently KIT levels. Altogether, our findings demonstrate that LIX1 contributes to GIST aggressive potential by modulating YAP1/TAZ and KIT levels, a process that depends on mitochondrial remodeling. Our work brings new insights into the mechanisms that could be targeted in tumors in which YAP1 and TAZ are implicated.

cancer biology↗

bioRxiv2019

Ultra-Conserved Elements and morphology reciprocally illuminate conflicting phylogenetic hypotheses in Chalcididae (Hymenoptera, Chalcidoidea)

Recent technical advances combined with novel computational approaches promised the acceleration of our understanding of the tree of life. However, when it comes to hyperdiverse and poorly known groups of invertebrates, studies are still scarce. As published phylogenies will be rarely challenged by future taxonomists, careful attention must be paid to potential analytical bias. We present the first molecular phylogenetic hypothesis for the family Chalcididae, an emblematic group of parasitoid wasps, with a representative sampling (144 ingroups and 7 outgroups) that covers all described subfamilies and tribes and 82% of the known genera. Analyses of 538 Ultra-Conserved Elements (UCEs) with supermatrix (RAxML and IQTREE) and gene-tree reconciliation approaches (ASTRAL, ASTRID) resulted in highly supported topologies in overall agreement with morphology but reveal conflicting topologies for some of the deepest nodes. To resolve these conflicts, we explored the phylogenetic tree space with clustering and gene genealogy interrogation methods, analyzed marker and taxon properties that could bias inferences and performed a thorough morphological analysis (130 characters encoded for 40 taxa representative of the diversity). This joint analysis reveals that UCEs enable attainment of resolution between ancestry and convergent /divergent evolution when morphology is not informative enough, but also shows that a systematic exploration of bias with different analytical methods and a careful analysis of morphological features is required to prevent publication of artefactual results. We highlight a GC-content bias for ML approaches, an artefactual mid-point rooting of the ASTRAL tree and a deleterious effect of high percentage of missing data on gene tree reconciliation methods. Based on the results we propose a new classification of the family into eight subfamilies and 10 tribes that lay the foundation for future studies on the evolutionary history of Chalcididae.

evolutionary biology↗