Biology subjects

Belliardo, C.

Publications and source records attributed to Belliardo, C..

4 recordsLinked to original sources

bioRxiv2026

An NR2F1-dependent retinoic acid network controls retinal specialization in mice and reveals foveal hypoplasia in patients with BBSOAS

The molecular programs that establish specialized retinal regions during development are essential for high-acuity vision, yet how their disruption contributes to human visual disorders remains poorly understood. Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), caused by pathogenic variants in NR2F1 and characterized by visual impairment, provides an opportunity to investigate these mechanisms. Using single-cell RNA sequencing of three complementary Nr2f1 mouse models, including two carrying patient-specific mutations, we identified a shared Nr2f1-dependent transcriptional program enriched in retinoic acid (RA) pathway genes. Loss or mutation of Nr2f1 disrupted the spatial organization of RA signaling, most prominently by expanding the dorso-equatorial Cyp26a1 expression domain into ventral retina and reducing ventral determinants such as Vax2. These molecular changes were associated with altered dorso-ventral distribution of S- and M-opsin-expressing cone photoreceptors. We further demonstrate that human NR2F1 binds a conserved regulatory region upstream of CYP26A1, supporting its direct role in regulating local RA availability. Finally, high-resolution optical coherence tomography in individuals with BBSOAS revealed reproducible foveal abnormalities, including a smaller and shallower foveal pit and increased central retinal thickness, consistent with foveal hypoplasia. These findings uncover a previously unrecognized retina-intrinsic component of BBSOAS visual pathology and establish an NR2F1-RA/CYP26A1 regulatory axis linking developmental retinal regionalization to human foveal specialization.

developmental biology↗

bioRxiv2025

Accurate MAG reconstruction from complex soil microbiome through combined short- and HiFi long-reads metagenomics

BackgroundAdvances in high-fidelity long-read (HiFi-LR) sequencing technologies have opened new opportunities to explore the microbial genomic diversity of complex environments, such as soils. While short-read (SR) sequencing has enabled broad insights at the gene level, the limited read length constrains the reconstruction of complete genomes. HiFi-LRs, in contrast, improve assembly continuity and completeness, supporting higher-resolution taxonomic and functional annotation. However, the cost and relatively low throughput of HiFi-LR sequencing can limit genome recovery--particularly at the binning stage, where coverage depth is critical. In this study, we assess the benefit of combining HiFi-LR and SR sequencing for genome-resolved characterization of a soil microbiome. ResultsWe generated metagenomic data for a tunnel-cultivated soil sample using high coverage Illumina SRs as well as a combination of two HiFi-LR sequencing platforms (PacBio Sequel II and PacBio Revio). We found that assemblies generated from pooled HiFi-LR data alone exhibited higher completeness compared to those from ultra-deep SR data. Incorporating SR-derived coverage information for the binning of HiFi-LR contigs further increased both the number and quality of recovered metagenome-assembled genomes (MAGs), with a 24% increase in MAG recovery (313 vs. 252) and lower contamination levels (116 vs. 132 contaminated bins; mean 7.09 vs. 8.07), compared to using HiFi-LR data alone. This approach enabled the recovery of 61 additional MAGs, including 67% of low-abundance and taxonomically diverse lineages such as Archaea, representing 36 novel lineages. ConclusionOur results demonstrate that integrating HiFi-LR and SR sequencing markedly enhances genome recovery and binning accuracy in a highly diverse environment such as soil. The hybrid approach employed leverages the strengths of both technologies, leading to more contiguous assemblies and enabling the recovery of a broader range of genomes, including low-abundance and taxonomically diverse taxa. While factors such as sequencing depth, cost, and DNA quality remain important considerations, our study provides practical guidance for designing future soil metagenomics projects and underscores the value of adopting long-read technologies for more comprehensive characterization of complex microbial communities.

genomics↗

bioRxiv2024

Functional carbohydrate-active enzymes acquired by horizontal gene transfer from plants in the whitefly Bemisia tabaci

Carbohydrate-active enzymes (CAZymes) involved in the degradation of plant cell walls and/or the assimilation of plant carbohydrates for energy uptake are widely distributed in microorganisms. In contrast, they are less frequent in animals, although there are exceptions, including examples of CAZymes acquired by horizontal gene transfer (HGT) from bacteria or fungi in several of phytophagous arthropods and plant-parasitic nematodes. Although the whitefly Bemisia tabaci is a major agricultural pest, knowledge of HGT-acquired CAZymes in this phloem-feeding insect of the Hemiptera order (subfamily Aleyrodinae) is still lacking. We performed a comprehensive and accurate detection of HGT candidates in B. tabaci and identified 136 HGT events, 14 of which corresponding to CAZymes. The B. tabaci HGT-acquired CAZymes were not only of bacterial or fungal origin, but some were also acquired from plants. Biochemical analysis revealed that members of the glycoside hydrolase families 17 (GH17) and 152 (GH152) acquired from plants are functional beta-glucanases with different substrate specificities, suggesting distinct roles. These two CAZymes are the first characterized GH17 and GH152 glucanases in an animal. We identified a lower number of HGT events in the related Aleyrodinae Trialeurodes vaporariorum, with only three HGT-acquired CAZymes, including a GH152 glucanase, with phylogenetic analysis suggesting a unique HGT event in the ancestor of the Aleyrodinae. Another GH152 CAZyme, most likely independently acquired from plants, was also identified in two plant cell-feeding insects of the Thysanoptera order, highlighting the importance of plant-acquired CAZymes in the biology of piercing-sucking insects. Significance statementCarbohydrate-active enzymes (CAZymes) are crucial for sugar metabolism. Those involved in plant cell wall degradation are usually absent from animal genomes. In this study, we explored CAZyme repertoires in the genomes of several insects: the phloem-feeding whitefly Bemisia tabaci, a major agricultural pest, and the related greenhouse whitefly Trialeurodes vaporariorum, as well as two Thysanoptera species that feed on plant cell contents. We identified several cases of CAZymes acquired from plant via horizontal gene transfer in the genome of these insects. Notably, we showed that two B. tabaci CAZymes of plant origin function as glucanases with distinct substrate specificities, potentially helping the insect to overcome plant defenses. Overall, these findings enhance our understanding of how the ability to feed on plants evolved in insects.

evolutionary biology↗

bioRxiv2021

Improvement of eukaryotic proteins prediction from soil metagenomes

BackgroundDuring the last decades, shotgun metagenomics and metabarcoding have highlighted the diversity of microorganisms from environmental or host-associated samples. Most assembled metagenome public repositories use annotation pipelines tailored for prokaryotes regardless of the taxonomic origin of contigs and metagenome-assembled genomes (MAGs). Consequently, eukaryotic contigs and MAGs, with intrinsically different gene features, are not optimally annotated, resulting in an incorrect representation of the eukaryotic component of biodiversity, despite their biological relevance. ResultsUsing an automated analysis pipeline, we have filtered 7.9 billion of contigs from 6,873 soil metagenomes in the IMG/M database of the Joint Genome Institute to identify eukaryotic contigs. We have re-annotated genes using eukaryote-tailored methods, yielding 8 million eukaryotic proteins. Of these, 5.6 million could be traced back to non-chimeric higher confidence eukaryotic contigs. Our pipeline improves eukaryotic proteins completeness, contiguity and quality. Moreover, the better quality of eukaryotic proteins combined with a more comprehensive assignment method improves the taxonomic annotation as well. ConclusionsUsing public soil metagenomic data, we provide a dataset of eukaryotic soil proteins with improved completeness and quality as well as a more reliable taxonomic annotation. This unique resource is of interest for any scientist aiming at studying the composition, biological functions and gene flux in soil communities involving eukaryotes. O_TEXTBOXKey Points O_LIEukaryotic micro-organisms have key roles in soil microbial communities and ecosystems. C_LIO_LIEukaryotic genes and proteins are incorrectly represented in metagenomic libraries due to inappropriate methods dedicated to prokaryotes. C_LIO_LIWe have improved the quality and completeness of the de novo proteins prediction and taxonomic annotation of eukaryotic organisms from soil or plant-associated microbiome. C_LI C_TEXTBOX

genomics↗