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Lavergne, A.

Publications and source records attributed to Lavergne, A..

6 recordsLinked to original sources

Cross-Continental Analysis of Vampire Bat Betaherpesvirus Reveals Limited Interference Among Strains and Local Geographic Spread

Desmodus rotundus Betaherpesvirus (DrBHV) is a candidate vector for a transmissible vaccine targeting the circulation of rabies virus within its vampire bat reservoir. Studies assessing the potential for DrBHV as a vector have not considered its geographic range, potential for transboundary spread or how the diversity of wildtype DrBHV in natural bat populations might impede the spread of a modified vaccine strain. Here, by sequencing DrBHVs from vampire bats spanning 15 regions across 7 rabies-affected countries in Latin America and the Caribbean, we characterise the continent-scale distribution of DrBHV diversity and demonstrate widespread and apparently unconstrained co-infection. DrBHV occurred in all regions, forming a monophyletic clade consistent with a single introduction to vampire bats or host-virus co-speciation rather than frequent host switching. Phylogeographic analyses revealed cross-boundary spread that was predicted by geographic proximity. We identified 50 putative DrBHV strains and 79% of DrBHV-infected bats harboured multiple strains. No strains were over- or under-represented in co-infection and co-infections occurred proportionately to local strain prevalence. Whether strains circulated in given populations was predominantly driven by the geographic proximity of other populations containing that strain. The evolutionary relatedness of strains constrained neither rates of co-infection within individuals nor whether strains co-circulated within regions, suggesting vaccine vectors might be locally sourced rather than requiring imported, divergent strains to ameliorate interference. These results support the viability of DrBHV-vectored vaccines for mitigating rabies virus across Latin America and the Caribbean, despite widespread circulation of wildtype viruses.

genomics↗

Single-cell transcriptomics reveals transcriptional diversity of sea cucumber perivisceral fluid coelomocytes

Echinoderms possess a complex immune system, primarily relying on coelomocytes - immune cells circulating in coelomic fluids. Over the last few decades, various coelomocytes have been described based on morphological features, with holothuroids exhibiting the highest diversity of cell morphotypes among the different echinoderm classes. However, while the overall immune function of these cells is broadly accepted, their respective functions remain unclear, and molecular data specific to the different cell types are still limited in the literature. In this study, we address this gap in functional information and molecular data by using single-cell RNA sequencing (scRNA-seq) on coelomocytes from the perivisceral fluid of Holothuria forskali. We identified 10 distinct clusters, each assumed to correspond to a distinct transcriptional coelomocyte population. Among these, cluster 0 occupies a central position relative to the others, suggesting it may represent "progenitor cells", whereas cluster 6 is markedly divergent from all other clusters. Functional enrichment analyses revealed that some clusters ensure key immune functions, including pathogen recognition, phagocytosis, complement activation and redox balance regulation. In addition, examination of the processed samples under a microscope confirms the presence of a small proportion of recently discovered carotenocytes (7.0%) in the perivisceral fluid, a cell type rich in carotenoids. By using transcriptomics data previously obtained for this cell type by bulk RNA sequencing (bRNA-seq), it was possible to confidently identify cluster 6 as carotenocytes and provide further insights into their gene expression. While further analyses are needed to link other clusters to the different morphotypes previously described in the literature, this pioneer study presents preliminary data on the functional diversity of holothuroid coelomocytes, which could be of broad interest for a better understanding of holothuroid immunity as well as for the study of immune cell lineage evolution across deuterostomes.

evolutionary biology↗

A DNA barcode library for Culex mosquitoes (Diptera: Culicidae) of South America with the description of two cryptic species of subgenus Melanoconion

The genus Culex is one of the most diverse in the world and includes numerous known vector species of parasites and viruses to humans. Morphological identification of Culex species is notoriously difficult and rely mostly on the examination of properly dissected male genitalia which largely prevents female and immature identification during entomological, ecological or arboviral surveys. The aims of this study were (i) to establish a DNA barcode library for Culex mosquitoes of French Guiana based on the mitochondrial gene cytochrome c oxidase I (COI) marker, (ii) to compare three approaches of molecular delimitation of species to morphological identification, and (iii) to test the effectiveness of the COI marker at a broader geographical scale across South America. Mosquitoes used in this study were sampled in French Guiana between 2013 and 2023. We provide 246 COI sequences for 90 morphologically identified species of Culex, including five new country records and two newly described species. Overall, congruence between morphological identification and molecular delimitations using the COI barcode were high. The Barcode of Life Data clustering approach into Barcode Index Numbers gives the best result in terms of species delimitation, followed by the muti-rate Poisson Tree Processes and the Assemble Species by Automatic Partitioning methods. Inconsistencies between morphological identification and molecular delimitation can be explained by introgression, incomplete lineage sorting, imperfect taxonomy or the effect of the geographical scale of sampling. This increases by almost two-fold the number of mosquito species for which a DNA barcode is available in French Guiana, including 75% of the species of Culex currently known in the territory. Finally, this study confirms the usefulness of the COI barcode in identifying Culex mosquitoes of South America, but also points the limits of this marker for some groups of species within the subgenera Culex and Melanoconion.

molecular biology↗

Negative cell cycle regulation by Calcineurin is necessary for proper beta cell regeneration in zebrafish

Stimulation of pancreatic beta cell regeneration could be a therapeutic lead to treat diabetes. Unlike humans, the zebrafish can efficiently regenerate beta cells, notably from ductal pancreatic progenitors. To gain insight into the molecular pathways involved in this process, we established the transcriptomic profile of the ductal cells after beta cell ablation in the adult zebrafish. These data highlighted the protein phosphatase calcineurin as a new potential modulator of beta cell regeneration. We showed that calcineurin overexpression abolished the regenerative response, leading to glycemia dysregulation. On the opposite, calcineurin inhibition increased ductal cell proliferation and subsequent beta cell regeneration. Interestingly, the enhanced proliferation of the progenitors was paradoxically coupled with their exhaustion. This suggests that the proliferating progenitors are next entering in differentiation. Calcineurin appears as a guardian which prevents an excessive progenitor proliferation to preserve the pool of progenitors. Altogether, our findings reveal calcineurin as a key player in the balance between proliferation and differentiation to enable a proper beta cell regeneration.

developmental biology↗

A δ-cell subpopulation with a pro-β-cell identity confers efficient age-independent recovery in a zebrafish model of diabetes

Restoring damaged {beta}-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study {beta}-cells arising following destruction. We show that most new insulin cells differ from the original {beta}-cells as they are Somatostatin+ Insulin+, but are nevertheless functional and normalize glycemia. These bihormonal cells are transcriptionally close to a subset of {delta}-cells in normal islets characterized by the expression of somatostatin 1.1 (sst1.1), the {beta}-cell genes pdx1, slc2a2 and gck, and the machinery for glucose-induced Insulin secretion. {beta}-cell destruction triggers massive sst1.1 {delta}-cell conversion to bihormonal cells. Our work shows that their pro- {beta}-cell identity predisposes this zebrafish {delta}-cell subpopulation to efficient age-independent neogenesis of Insulin-producing cells and provides clues to restoring functional {beta}-cells in mammalian diabetes models.

cell biology↗

Combined analysis of single cell RNA-Seq and ATAC-Seq data reveals regulatory toggles operating in native and iPS-derived retina.

We report the generation and analysis of single-cell RNA-Seq data (> 38,000 cells) from native and iPSC-derived murine retina at four matched developmental stages spanning the emergence of the major retinal cell types. We combine information from temporal sampling, visualization of 3D UMAP manifolds, pseudo-time and RNA velocity analyses, to show that iPSC-derived 3D retinal aggregates broadly recapitulate the native developmental trajectories. However, we show relaxation of spatial and temporal transcriptome control, premature emergence and dominance of photoreceptor precursor cells, and susceptibility of dynamically regulated pathways and transcription factors to culture conditions in iPSC-derived retina. We generate bulk ATAC-Seq data for native and iPSC-derived murine retina identifying [~]125,000 peaks. We combine single-cell RNA-Seq with ATAC-Seq information and obtain evidence that approximately half the transcription factors that are dynamically regulated during retinal development may act as repressors rather than activators. We propose that sets of activators and repressors with cell-type specific expression constitute "regulatory toggles" that lock cells in distinct transcriptome states underlying differentiation. We provide evidence supporting our hypothesis from the analysis of publicly available single-cell ATAC-Seq data for adult mouse retina. We identify subtle but noteworthy differences in the operation of such toggles between native and iPSC-derived retina particularly for the Etv1, Etv5, Hes1 and Zbtb7a group of transcription factors.

developmental biology↗