Biology subjects

Severac, D.

Publications and source records attributed to Severac, D..

13 recordsLinked to original sources

bioRxiv2026

Single-cell atlas reveals age-related cellular shifts underlying fibrosis in murine synovium

Aging is a major risk factor for joint disease, yet the impact of physiological aging on the synovium remains poorly defined. Here we generate a single-cell atlas of murine ankle synovium across age and identify the sublining stromal-myeloid niche as a major site of age-associated remodeling. Aging shifted fibroblast states toward oxidative stress and matrix-remodeling programs, accompanied by sublining collagen accumulation, reduced cellularity, and loss of THY1+ sublining fibroblasts. In parallel, resident synovial macrophages exhibited altered inflammatory and phagocytic responses together with a preferential decline in TIM4+VSIG4- sublining macrophages, without overt local myeloid expansion despite systemic inflammaging. Macrophage depletion experiments further supported a link between sublining macrophages and extracellular matrix homeostasis. Together, these findings provide a reference framework for synovial aging and uncover niche-specific stromal and macrophage alterations associated with aging.

physiology↗

bioRxiv2026

APPNL-F knock-in Alzheimer's Disease model mice reveal etiological convergence of aging and amyloidosis

Alzheimers disease (AD) is the leading cause of dementia worldwide, with a steadily increasing prevalence. Despite the advent of some plaque-degrading therapies, early intervention strategies are still suboptimal, largely due to an incomplete understanding of how early pathological events of amyloid-{beta} (A{beta}) plaque deposition entail or accompany the neuroinflammatory processes that ensue. The APPNL-F mouse line is a second-generation endogenous-promoter knock-in AD model that represents a valuable tool to dissect disease mechanisms and evaluate therapeutic strategies. However, the early prodromal stage remains poorly characterized. Here we performed in-depth analyses in both homozygous (APPNL-F/NL-F) and heterozygous (APPNL-F/WT) mice at 3, 6, 9 and 12 months of age. Among a battery of behavioural tests, the first phenotype was observed at 9 months with defects in spatial memory. Using hypersensitive MSD-ELISA technology assays we quantified distinct A{beta} species and found that A{beta}42 oligomers, protofibrils, and fibrillar aggregates were detectable as early as 6 months of age in homozygous APPNL-F/NL-F mice. By 9 months, their A{beta}42 levels increased markedly and overt A{beta} plaques were detected, histologically associated with recruited glial cells. Targeted RT-qPCR analysis of neuroinflammation-related genes in the cortex also identified 9 months as a molecular tipping point in these middle aged APPNL-F mice. To characterize the etiological signal transduction at the cellular level, we isolated microglia, the brain resident immune cells, whose contribution to AD pathogenesis is now well established. Sequencing around 5,000 individual cells from both 12-month-old APPNL-F/NL-F and APPWT/WT CD11b+ myeloid cells revealed that the buildup of amyloidosis was associated with an accelerated shift of microglia from a homeostatic toward a senescent-like state. Together, these findings highlight the 6-12 month period of the APPNL-F/NL-F model as a powerful system to study the interdependence between microglial senescence and amyloidosis in driving AD progression.

neuroscience↗

bioRxiv2023

Analysis of a shark reveals ancient habenular asymmetries in gnathostomes and points to Wnt regulation as a driving force in their diversification

The origin of left-right asymmetries in the vertebrate habenula remains largely unknown. Using a transcriptomic approach, we show that in a cartilaginous fish, the catshark Scyliorhinus canicula, habenulae exhibit marked asymmetries both in their medial and their lateral component. Comparisons across gnathostomes suggest that asymmetries in the catshark lateral habenulae reflect an ancestral gnathostome trait, independently lost in tetrapods and neopterygians. Analysis of the mechanisms underlying their formation highlights an essential role of Wnt signaling. Wnt activity is submitted to a dynamic, asymmetric regulation during habenula development, with a Nodal dependent left repression at a stage when precursors for lateral habenulae have exited cell cycles. Pharmacological treatments during this time window reveal that Wnt signaling promotes lateral right neuronal identities in the right lateral habenula, while its repression by Nodal in the left one promotes lateral left neuronal identities. Based on comparisons with the zebrafish and the mouse, we propose that habenular asymmetry formation and diversification in gnathostomes involve the same developmental logic, relying on a conserved temporal regulation of neurogenesis, shaping neuronal identities on both sides, and its modification by a dynamic Wnt activity, right-restricted in the ancestral state and prone to variations in time and space during evolution.

developmental biology↗

bioRxiv2022

Divergence of olfactory receptors associated with the evolution of assortative mating and reproductive isolation in mice

AO_SCPLOWBSTRACTC_SCPLOWDeciphering the genetic bases of behavioural traits is essential to understanding how they evolve and contribute to adaptation and biological diversification, but it remains a substantial challenge, especially for behavioural traits with polygenic architectures. In this study, we developed a population genomics approach coupled with functional predictions to address the evolution and genetic basis of olfactory-based assortative mate preferences in the house mouse, suspected to have evolved as a response to selection against hybridisation. We used whole genome resequencing data and the C2 statistic of the program BO_SCPLOWAYC_SCPLOWPO_SCPLOWASSC_SCPLOW, which contrasts allele frequencies corrected for population structure, to characterize genetic differentiation between sets of populations with strong contrast in behaviour (expressing or not assortative mate preferences) and we identified some regions of the genome showing the expected significant and consistent association with behavioural divergence. A series of Olfactory and Vomeronasal Receptor genes, among the most differentiated genomic regions and in line with functional predictions, stand out as the prime candidates underlying this olfactory-based behavioural divergence. These genes form large gene clusters in the genome, with two main candidate clusters extending up to 1.8 Mb. Variant analyses indicate a potential dual role of regulatory and protein-coding changes in the evolution of choosiness. This study shows that combining expectations on the genomic patterns of divergence with functional expectations represents a promising route to unravelling the genetic architecture of complex trait variation and provides novel insights into the role of olfactory and vomeronasal receptors in mammal adaptation and speciation.

evolutionary biology↗

bioRxiv2021

The regenerative response of cardiac interstitial cells

Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction. Currently, it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration. To understand how interstitial cells behave during cardiac regeneration, we performed single-cell RNA sequencing (scRNA-seq) of regenerating zebrafish hearts. Using a combination of immunohistochemistry, chemical inhibition and novel transgenic animals, we were able to investigate the role of cell type specific responses during cardiac regeneration. This approach allowed us to identify a number of important regenerative mechanisms within the interstitial cell populations. Here, we provide here a detailed insight into how interstitial cells behave during cardiac regeneration and identify a number of novel features of these cells which will serve to increase our understanding of how this process could eventually be induced in humans.

cell biology↗

bioRxiv2021

Transcriptomic, epigenetic and metabolic characterization of the pluripotency continuum in rabbit preimplantation embryos

Despite the growing interest in the rabbit model for developmental and stem cell biology, the characterization of embryos at the molecular level is still poorly documented. We conducted a transcriptome analysis of rabbit pre-implantation embryos from E2.7 (morula stage) to E6.6 (early primitive streak stage) using bulk and single-cell RNA-sequencing. In parallel, we studied oxidative phosphorylation and glycolysis and analysed active and repressive epigenetic modifications during blastocyst formation and expansion. We generated a transcriptomic, epigenetic, and metabolic map of the pluripotency continuum in rabbit preimplantation embryos and identified novel markers of naive pluripotency that might be instrumental for deriving naive pluripotent stem cell lines. Although the rabbit is evolutionarily closer to mice than to primates, we found that the transcriptome of rabbit epiblast cells shares common features with that of humans and non-human primates. Summary StatementRabbit preimplantation embryos share characteristics with human and monkey embryos with respect to timing of early lineage segregation and expression of marker genes for naive and primed pluripotency.

developmental biology↗

bioRxiv2021

H3K9me2 genome-wide distribution in the holocentric insect Spodoptera frugiperda (Lepidoptera: Noctuidae)

BackgroundEukaryotic genomes are packaged by Histone proteins in a structure called chromatin. There are different chromatin types. Euchromatin is typically associated with decondensed, transcriptionally active regions and heterochromatin to more condensed regions of the chromosomes. Methylation of Lysine 9 of Histone H3 (H3K9me) is a conserved biochemical marker of heterochromatin. In many organisms, heterochromatin is usually localized at telomeric as well as pericentromeric regions but can also be found at interstitial chromosomal loci. This distribution may vary in different species depending on their general chromosomal organization. Holocentric species such as Spodoptera frugiperda (Lepidoptera: Noctuidae) possess dispersed centromeres instead of a monocentric one and thus no observable pericentromeric compartment. To identify the localization of heterochromatin in such species we performed ChIP-Seq experiments and analyzed the distribution of the heterochromatin marker H3K9me2 in the Sf9 cell line and whole 4th instar larvae (L4) in relation to RNA-Seq data. ResultsIn both samples we measured an enrichment of H3K9me2 at the (sub) telomeres, rDNA loci, and satellite DNA sequences, which could represent dispersed centromeric regions. We also observed that density of H3K9me2 is positively correlated with transposable elements and protein-coding genes. But contrary to most model organisms, H3K9me2 density is not correlated with transcriptional repression. ConclusionThis is the first genome-wide ChIP-Seq analysis conducted in S. frugiperda for H3K9me2. Compared to model organisms, this mark is found in expected chromosomal compartments such as rDNA and telomeres. However, it is also localized at numerous dispersed regions, instead of the well described large pericentromeric domains, indicating that H3K9me2 might not represent a classical heterochromatin marker in Lepidoptera.

genomics↗

bioRxiv2021

Autoregulation dependent and independent mechanisms are responsible for the systemic control of nodule formation by the plant N demand

In legumes interacting with rhizobia the formation of symbiotic organs responsible for the acquisition of atmospheric nitrogen is depending of the plant nitrogen (N) demand. We discriminated between local and systemic impact of nitrogen on nodule formation using Medicago truncatula plants cultivated in split-root systems. We obtained evidence of the control of nodule formation by whole plant systemic N-satisfaction signaling but obtained little evidence of a local control by mineral nitrogen. We characterized the impact of systemic N signaling on the root transcriptome reprogramming associated to nodule formation. We identified, large genes clusters displaying common expression profiles in response to systemic N signaling enriched in particular fonctions required during these biological processes. We found evidence of a strong effect of SUNN in the control by systemic N signaling of many genes involved in the early interaction with rhizobium as well as organogenesis supporting a role of autoregulation pathway in systemic N signaling. However, we also found evidence that major SUNN independent systemic N signaling controls were maintained in the mutant. This study shed light on the unexpected high complexity of the control of nodule formation by systemic N signaling, that probably involves multiple pathways.

plant biology↗

bioRxiv2019

Spodoptera frugiperda transcriptional response to infestation by Steinernema carpocapsae

Steinernema carpocapsae is an entomopathogenic nematode (EPN) used in biological control of agricultural pest insects. It enters the hemocoel of its host via the intestinal tract and releases its symbiotic bacterium Xenorhabdus nematophila, which kills the insect in less than 48 hours. Although several aspects of its interactions with insects have been extensively studied, still little is known about the immune and physiological responses of its different hosts. In order to improve this knowledge, we examined the transcriptional responses to EPN infestation of the fat body, the hemocytes and the midgut in the lepidopteran pest model Spodoptera frugiperda (Lepidoptera: Noctuidae).\n\nOur results indicate that the tissues poorly respond to the infestation at an early time post-infestation of 8 h, even though the proliferation of the bacterial symbiont within the hemocoel is detected. Only 5 genes are differentially expressed in the fat body of the caterpillars. However, strong transcriptional responses are observed at a later time point of 15 h post-infestation in all three tissues. While few genes are differentially expressed in the midgut, tissue-specific panels of induced metalloprotease inhibitors, immune receptors and antimicrobial peptides together with several uncharacterized genes are up-regulated in the fat body and the hemocytes. In addition, among the most up-regulated genes, we identified new potential immune effectors, unique to Lepidoptera, for which we present evidence of acquisition by Horizontal Gene Transfer from bacteria.\n\nAltogether, these results pave the way for further functional studies of the mobilized genes involvement in the interaction with the EPN.\n\nAuthor summaryThe Fall Armyworm, Spodoptera frugiperda, is a major agricultural pest. The caterpillars cause extensive damage to crops of importance such as corn, rice, sorghum and cotton. Originally from the Americas, it is currently becoming invasive in other parts of the world, first in Africa in 2016, then in India and now in south-east Asia. Programs of biological control against insect pests are increasingly encouraged around the world and include the use of pathogens. Entomopathogenic nematodes such as Steinernema carpocapsae are already commercialized as organic pesticides. These nematodes live in the soil and enter the body of their insect preys. Once within the insects, they release their symbiotic bacteria (Xenorhabdus nematophila in this case), which infect and kill the host in a few hours. The nematodes can then feed on the dead insects, reproduce and resume their life cycle. It is a major challenge to understand how EPN achieve their pathogenicity as well as how the insects can resist them. Here we provide the foundation for such an interaction between EPN and a Lepidoptera. We analyzed the dynamic of transcriptional response in three insect tissues (midgut, fat body and hemocytes) upon infestation by EPN. Not many studies have been performed genome-wide on such an interaction, and none on a Lepidopteran model of economical importance. Our transcriptomic approach revealed some specificities of the Lepidopteran defense mechanisms. In particular, we discovered a set of genes, acquired in Lepidoptera from bacteria by Horizontal Gene Transfer, that probably encode proteins with antibiotic activity.

genomics↗

bioRxiv2018

Differential immune gene expression associated with contemporary range expansion of two invasive rodents in Senegal

BackgroundBiological invasions are major anthropogenic changes associated with threats to biodiversity and health. What determines the successful establishment of introduced populations still remains unsolved. Here we explore the appealing assertion that invasion success relies on immune phenotypic traits that would be advantageous in recently invaded sites. ResultsWe compared gene expression profiles between anciently and recently established populations of two major invading species, the house mouse Mus musculus domesticus and the black rat Rattus rattus, in Senegal. Transcriptome analyses revealed respectively 364 and 83 differentially expressed genes along the mouse and rat invasion routes. Among them, 20.0% and 10.6% were annotated with functions related to immunity. All immune-related genes detected along the mouse invasion route were over-expressed in recently invaded sites. Genes of the complement activation pathway were over-represented. Results were less straightforward when considering the black rat as no particular immunological process was over-represented. ConclusionsWe revealed changes in transcriptome profiles along invasion routes. Patterns differed between both invasive species. These changes potentially be driven by increased infection risks in recently invaded sites for the house mouse and stochastic events associated with colonization history for the black rat. These results provide a first step in identifying the immune ecoevolutionary processes potentially involved in invasion success.

ecology↗

bioRxiv2018

The genomic basis of colour pattern polymorphism in the harlequin ladybird

Many animal species are comprised of discrete phenotypic forms. Understanding the genetic mechanisms generating and maintaining such phenotypic variation within species is essential to comprehending morphological diversity. A common and conspicuous example of discrete phenotypic variation in natural populations of insects is the occurrence of different colour patterns, which has motivated a rich body of ecological and genetic research1-6. The occurrence of dark, i.e. melanic, forms, displaying discrete colour patterns, is found across multiple taxa, but the underlying genomic basis remains poorly characterized. In numerous ladybird species (Coccinellidae), the spatial arrangement of black and orange patches on adult elytra varies wildly within species, forming strikingly different complex colour patterns7,8. In the harlequin ladybird Harmonia axyridis, more than 200 distinct colour forms have been described, which classic genetic studies suggest result from allelic variation at a single, unknown, locus9,10. Here, we combined whole-genome sequencing, population genomics, gene expression and functional analyses, to establish that the gene pannier controls melanic pattern polymorphism in H. axyridis. We show that pannier, which encodes an evolutionary conserved transcription factor, is necessary for the formation of melanic elements on the elytra. Allelic variation in pannier leads to protein expression in distinct domains on the elytra, and thus determines the distinct colour patterns in H. axyridis. Recombination between pannier alleles may be reduced by a highly divergent sequence of ca. 170 kb in the cis-regulatory regions of pannier with a 50 kb inversion between colour forms. This likely helps maintaining the distinct alleles found in natural populations. Thus we propose that highly variable discrete colour forms can arise in natural populations through cis-regulatory allelic variation of a single gene.

evolutionary biology↗

bioRxiv2018

Transcriptomic analyses with the progress of symbiosis in ‘crack-entry’ legume Arachis hypogaea highlight its contrast with ‘Infection thread’ adapted legumes

In root-nodule symbiosis, rhizobial invasion and nodule organogenesis is host controlled. In most legumes, rhizobia enter through infection-threads and nodule primordium in the cortex is induced from a distance. But in dalbergoid legumes like Arachis hypogaea, rhizobia directly invade cortical cells through epidermal cracks to generate the primordia. Herein we report the transcriptional dynamics with the progress of symbiosis in A. hypogaea at 1dpi: invasion; 4dpi: nodule primordia; 8dpi: spread of infection in nodule-like structure; 12dpi: immature nodules containing rod-shaped rhizobia; and 21dpi: mature nodules with spherical symbiosomes. Expression of putative orthologue of symbiotic genes in crack-entry legume A. hypogaea was compared with infection thread adapted model legumes. The contrasting features were (i) higher expression of receptors like LYR3, EPR3 as compared to canonical NFRs (ii) late induction of transcription factors like NIN, NSP2 and constitutive high expression of ERF1, EIN2, bHLH476 and (iii) induction of divergent pathogenesis responsive PR-1 genes. Additionally, symbiotic orthologues of SymCRK, FLOT4, ROP6, RR9, NOOT and SEN1 were not detectable and microsynteny analysis indicated the absence of RPG and DNF2 homologues in diploid parental genomes of A. hypogaea. The implications are discussed and a molecular framework that guide crack-entry symbiosis in A. hypogaea is proposed.

plant biology↗

bioRxiv2018

Transcriptomic response to host and non-host plants during oviposition in two closely related moth species

We present here a comprehensive analysis of the transcriptomic response to plant environments in ovipositing females of two sibling species of phytophagous moths affiliated to different host ranges: the European corn borer (ECB) and the adzuki bean borer (ABB). We first assembled and annotated a de novo reference transcriptome based on a high throughput RNA sequencing of females placed in different plant environments, then we measured differences in gene expression between ECB and ABB, and also within each moth species between environments. We further related the differentially expressed (DE) genes to the host preference in ECB and ABB and highlighted the functional categories involved. More specifically, we conducted an analysis on chemosensory genes previously characterized in ECB, ABB and other related Ostrinia species, as these genes are considered as good candidates for the host recognition before oviposition.\n\nOverall, we recorded more DE genes in ECB than in ABB samples, what could highlight the higher strength of the host specialization in ECB compared to ABB as observed at the behavioral level. We also noticed that the genes involved in the preference for their respective host were different between ECB and ABB. At the functional level, the response to plant environment in ECB and ABB during oviposition involved many processes, including the chemosensory repertoire as expected, but also metabolism of carbohydrates, lipids, proteins, and amino acids, detoxification mechanisms and immunity.\n\nAll together, our results allowed identifying genes and functions candidates for specialization and also for the species divergence between ECB and ABB. By ad-hoc categorization, we discriminated some genes responding to the environment with similar or divergent pattern in ECB and ABB. Among them, we highlighted new lines of research like carbohydrates metabolism or virus and retrovirus dynamics.

evolutionary biology↗