Biology subjects

Gilson, E.

Publications and source records attributed to Gilson, E..

15 recordsLinked to original sources

bioRxiv2026

Diversity, host-specificity, and environmental drivers of the coral reef eukaryome

Coral reefs are among the most diverse ecosystems on Earth, yet the diversity and structure of their associated microeukaryotic communities remain poorly resolved. We characterized reef-associated eukaryomes across 113 reefs spanning the Pacific Ocean using more than 6,300 samples from corals, seawater, and sediments during the Tara Pacific expedition. We identified [~]121,000 eukaryotic ASVs, revealing one of Earths largest undocumented reservoirs of eukaryotic diversity; over 80% of the recovered diversity was previously undetected in global ocean surveys and fewer than 2% of sequences matched reference databases. Reef habitats supported highly distinct communities, with sediments and seawater harboring 20-40-fold higher richness than corals. Unexpectedly, coral-associated communities across 29 host lineages were consistently dominated by small metazoans, particularly demosponges and maxillopods, identifying these taxa as pervasive and previously unrecognized components of coral eukaryomes alongside Apicomplexa. Across the Pacific, eukaryome composition was strongly structured by environmental gradients, with thermal stress emerging as the primary driver of community turnover. Together, these results identify coral reefs as a globally important reservoir of hidden eukaryotic diversity and reveal the reef eukaryome as a sensitive indicator of ecosystem reorganization under climate change.

systems biology↗

bioRxiv2026

Targeting the senescence-associated immune checkpoint GD3 ganglioside extends healthspan and blunt age-related diseases with sex-specific benefits.

The accumulation and impact of senescent cells in age-related diseases are increasingly characterized. However, the mechanisms underlying their accumulation and their causative role in age-associated pathologies remain poorly understood. We recently demonstrated that senescent cells can evade immune surveillance by regulating the expression of cell surface molecules such as the disialylated ganglioside GD3, which acts as a senescence-associated immune checkpoint (SIC) 1-3. Targeting GD3 therefore represents a novel therapeutic opportunity for age-related diseases. Here, we examined the effects of short-term anti-GD3 antibody treatment in mid-life on aging and age-related diseases in male and female mice, revealing striking sex-specific benefits. Treatment improved healthspan, survival (+20%) and reduced non-cancer mortality in males, while in females it reduced cancer-specific mortality without significantly affecting overall survival. Anti-GD3 treatment also mitigated fibrosis in lung, liver, and kidney tissues with distinct sex-dependent responses. Importantly, these benefits persisted for over a year after treatment cessation. These findings suggest that GD3-targeted therapy holds promise as a precision approach for treating age-related diseases, with therapeutic outcomes that depend critically on biological sex.

cell biology↗

bioRxiv2025

Molecular mechanism decipher of Alzheimer's disease based on single-cell RNA-seq information

BackgroundAlzheimers disease (AD) is a most common age-related neurodegenerative disease with no effective treatments, is one of the leading contributions to global disease burden. AD is represented by complicated biological mechanisms and complexity of brain tissues, often manifested histologically by the parenchymal deposition of amyloid-beta (A{beta}) plaques, the formation of neurofibrillary tangles and neuroinflammation. The etiology of AD is likely due to complex interactions among different brain cell types leading to interconnected cellular pathologies. Single-cell RNA sequencing (RNA-seq) technologies enable unbiased characterization of cell types and states, transitions from normal to disease and responses to therapies, providing an effective tool to systematically resolve cellular heterogeneity in AD. MethodsIn this study, to investigate the molecular mechanisms of AD, we collected single cell RNA-seq data of disease and control samples and designed an precise computational analysis pipeline for the dataset. We further proposed a consensus non-negative matrix factorization model to extract disease cellular gene expression programs. ResultsAccording to the computational pipeline, we get the most disease-related sub-clusters, cellular process gene expression programs, and disease-related gene programs. We further investigated the enrichment pathways of disease gene programs. DiscussionThis research might provide a cell type specific gene program targets therapeutic approach to combat the disease. HighlightsO_LIWe designed a consensus non-negative matrix factorization method, which could extract cellular process gene expression programs, and disease-related gene programs. C_LIO_LIWe further investigated the enrichment pathways of the most disease-related sub-clusters. C_LIO_LIWe provide a cellular foundation for a new perspective on AD molecular mechanism that informs personalized therapeutic development, targeting the disease-related gene program. C_LI

bioinformatics↗

bioRxiv2025

The adaptive molecular landscape of reprogrammed telomeric sequences

Telomeric sequences vary across the tree of life and intimately co-evolve with telomere-binding protein complexes. However, the molecular mechanisms allowing organisms to adapt to new telomeric sequences are difficult to gauge from extant species. Here, we reprogrammed multiple yeast lines to human-like telomeric repeats to unveil their molecular and fitness response to novel telomeres. Initially, the exchange of telomere sequences resulted in genome instability, proteome remodelling and severe fitness decline. However, adaptive evolution experiments selected for repeated mutations that drove adaptation to the humanized telomeres. These consisted of the recurrent amplification of the telomere-binding protein TBF1, by complex aneuploidies, or in repeated mutations that attenuate the DNA damage response. Overall, our results outline a response that defines the adaptive molecular landscape to novel telomeric sequences.

evolutionary biology↗

bioRxiv2025

The ganglioside GD3 and its Synthase (ST8SIA1) as novel senescence markers associated with osteoarthritis

Osteoarthritis (OA), is the most common age-induced degenerative joint disease. It is associated with synovial inflammation, subchondral bone remodeling and cartilage degradation. One of the significant emerging causes of OA progression is senescent cell accumulation within the joint compartment during lifespan. Currently, there are no therapeutic approaches nor stratification tools that rely on the senescence burden in OA. In this study, we identified the b-series ganglioside 3 (GD3) as new senescent cell surface marker associated with OA. Joint RNA sequencing analysis revealed an increase expression of the GD3 synthase, ST8SIA1 in cartilage, synovial tissue, and subchondral bone marrow from OA patients compared to healthy donors. Moreover, we revealed a strong correlative association between the expression of ST8SIA1 and GD3 production with senescence hallmarks in an in vitro-induced 3D organotypic OA cartilage model but also with cartilage histological grading scores in human and preclinical murine OA joints. Anti-GD3 cell sorting showed that GD3-positive human OA chondrocytes or human OA synoviocytes are enriched in senescence and SASP markers compared to GD3-negative counterparts confirming that GD3 is a cell surface marker linked to the senescence stage. Intra-articular anti-GD3 antibody delivery in experimental OA model, reduced local expression of senescence and OA markers in association with a protection against OA-induced subchondral bone remodeling. Our research demonstrates a compelling linkage between ST8SIA1 gene, GD3 and senescence in OA pathology, revealing knowledge and perspectives for a better understanding and anti-senescence treatment of OA pathogenesis.

cell biology↗

bioRxiv2023

ProA and ProB repeat sequences shape genome organization, and enhancers open domains

Genome organization is partially conserved across cell types, yet its DNA-encoded determinants remain incompletely understood. Here we define ProA and ProB repeat sequences (RepSeqs) as two classes of cis-elements that promote A/euchromatin or B/heterochromatin compartment identity. We show that relative ProA/ProB density predicts Hi-C compartment profiles, indicating that compartmental propensity is largely encoded in sequence composition, and point to specific chromatin-based mechanisms underlying these effects. ProA RepSeqs are predominantly Alu elements, whereas ProB RepSeqs comprise young LINE-1s, selected ERVs, AT-rich microsatellites, and satellite repeats. RepSeqs of more indefinite character, including transcriptional enhancers, can switch between ProA and ProB functions to open or close chromatin domains in a context-dependent manner. In cancer, CpG methylation loss disproportionately impacts ProB RepSeqs, weakening the B compartment and thereby contributing to genome unfolding and cancer cell plasticity.

genetics↗

bioRxiv2022

Induction of telomerase in p21-positive cells counteracts capillaries rarefaction in aging mice lung

Telomerase is required for long-term cell proliferation and linked to stem cells. This is evident in the lung where short telomeres are associated with lung dysfunction. We constructed a mouse model in which the telomerase (Tert) is expressed from the p21Cdkn1a promoter. We found that this peculiar Tert expression curb age-related emphysema and pulmonary perivascular fibrosis in old mice. In old mice lungs, such Tert expression preferentially occurs in endothelial cells where it reduces the number of senescent endothelial cells. Remarkably, we report that Tert counteracts the age-related decline in capillary density. This was associated with an increased number of Cd34+ cells identified as a subclass of capillary cells with proliferative capacity. Expression of catalytically inactive Tert neither prevents the decline of capillary density in old mice nor protects against age-related emphysema and fibrosis. These findings reveal that telomerase decreases age-decline of pulmonary functions by sustaining microvasculature regeneration and outgrowth.

molecular biology↗

bioRxiv2022

From genome wide SNPs to genomic islands of differentiation: the quest for species diagnostic markers in two scleractinian corals, Pocillopora and Porites

Coral reefs are of paramount importance in marine ecosystems, where they provide support for a large part of the biodiversity. Being quite sensitive to global changes, they are therefore the prime targets for biodiversity conservation policies. However, such conservation goals require accurate species identification, which are notoriously difficult to get in these highly morphologically variable organisms, rich in cryptic species. There is an acute need for easy-to-use and resolutive species diagnostic molecular markers. The present study builds on the huge sequencing effort developed during the TARA Pacific expedition to develop a genotyping strategy to assign coral samples to the correct species within two coral genera (Porites and Pocillopora). For this purpose, we developed a technique that we called "Divergent Fragment" based on the sequencing of a less than 2kb long diagnostic genomic fragment determined from the metagenomic data of a subset of the corals collected. This method has proven to be rapid, resolvable and cost-effective. Sequencing of PCR fragments nested along the species diagnostic fragment allowed us to assign 232 individuals of the genus Pocillopora and 247 individuals of the genus Porites to previously identified independent genetic lineages (i.e. species). This genotyping method will allow to fully analyze the coral samples collected across the Pacific during the Tara Pacific expedition and opens technological perspectives in the field of population genomics-guided conservation.

evolutionary biology↗

bioRxiv2022

Disparate patterns of genetic divergence in three widespread corals across a pan-Pacific environmental gradient highlights species-specific adaptation trajectories.

Tropical coral reefs are among the worst affected ecosystems by climate change with predictions ranging between a 70-90% loss of reefs in the coming decades. Effective conservation strategies that maximize ecosystem resilience, and potential for recovery, must be informed by the accurate characterization of extant genetic diversity and population structure together with an understanding of the adaptive potential of keystone species. Here, we analyzed samples from the Tara Pacific Expedition (2016 to 2018) that completed an 18,000 km longitudinal transect of the Pacific Ocean sampling three widespread corals - Pocillopora meandrina, Porites lobata, and Millepora cf. platyphylla - across 33 sites from 11 islands. Using deep metagenomic sequencing of 269 colonies in conjunction with morphological analyses and climate variability data we can show that the sampled transect encompasses multiple morphologically cryptic species that exhibit disparate biogeographic patterns, and most importantly, distinct evolutionary patterns, despite exposure to identical environmental regimes. Our findings demonstrate on a basin-scale that evolutionary trajectories are species-specific and complex, and can only in part be predicted from the environment. This highlights that conservation strategies must integrate multi-species investigations to consider the distinct genomic footprints shaped by selection as well as the genetic potential for adaptive change.

genetics↗

bioRxiv2022

Open science resources from the Tara Pacific expedition across coral reef and surface ocean ecosystems

AbstractThe Tara Pacific expedition (2016-2018) sampled coral ecosystems around 32 islands in the Pacific Ocean and the ocean surface waters at 249 locations, resulting in the collection of nearly 58,000 samples. The expedition was designed to systematically study warm coral reefs and included the collection of corals, fish, plankton, and seawater samples for advanced biogeochemical, molecular, and imaging analysis. Here we provide a complete description of the sampling methodology, and we explain how to explore and access the different datasets generated by the expedition. Environmental context data were obtained from taxonomic registries, gazetteers, almanacs, climatologies, operational biogeochemical models, and satellite observations. The quality of the different environmental measures has been validated not only by various quality control steps but also through a global analysis allowing the comparison with known environmental large-scale structures. Such a wide released datasets opens the perspective to address a wide range of scientific questions.

ecology↗

bioRxiv2022

Pervasive gene duplications as a major evolutionary driver of coral biology

Over the last decade, several coral genomes have been sequenced allowing a better understanding of these symbiotic organisms threatened by climate change. Scleractinian corals are reef builders and are central to these ecosystems, providing habitat and food to a great diversity of species. In the frame of the Tara Pacific expedition, we generated two coral genomes, Porites lobata and Pocillopora meandrina with vastly improved contiguity that allowed us to study the functional organisation of these genomes. We annotated their gene catalog and report a relatively higher gene number (43,000 and 32,000 genes respectively) than that found in other public coral genome sequences. This finding is explained by a high number of tandemly duplicated genes (almost a third of the predicted genes). We show that these duplicated genes originate from multiple and distinct duplication events throughout the coral lineage. They contribute to the amplification of gene families, mostly related to immune system and disease-resistance, which we suggest to be functionally linked to coral host resilience. At large, we show the importance of duplicated genes to inform the biology of reef-building corals and provide novel avenues to understand and screen for differences in stress resilience.

genomics↗

bioRxiv2022

Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones

Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome-sequences and applied it to the sequenced 1011 S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Wild isolates are enriched in loss-of-function mutations in genes known to regulate telomere DNA length and the return of domesticated yeasts to a wild habitat coincides with shorter telomeres. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings suggest that budding yeasts telomere DNA length regulation might be shaped by ecological life-styles.

genomics↗

bioRxiv2021

Specific telomere protection ensured by FOXO3a upon genotoxic stress and during aging

Longevity is determined by diverse signaling pathways including telomere protection and homeostasis master regulators like FOXO3a. We previously showed that the telomeric repeat binding factor 2 (TRF2) expression decreases with age in human skeletal muscle and that, surprisingly, its loss in myofibers does not trigger telomere deprotection. We reveal here that in TERF2-compromised myotubes, FOXO3a is recruited to telomeres where it acts as a protective factor against ATM-dependent DNA damage activation. Moreover, we show that FOXO3a-telomere association increases with age in human skeletal muscle biopsies. In mitotic fibroblasts, the telomere protective properties of FOXO3a are operative if the cells are treated with bleomycin. The telomere function of FOXO3a does not require its Forkhead DNA binding domain but the CR2C. Overall, these findings demonstrate a direct connection between two key longevity pathways, FOXO3a and telomere protection. This unveils an unexpected higher level of integration in the regulation of longevity signaling pathway.

cell biology↗

bioRxiv2021

A ganglioside-based senescence-associated immune checkpoint

Senescent cells accumulate in aging tissues, and their elimination can favor healthy aging1-4. Therefore, therapeutic interventions targeting cellular senescence may be promising strategies for delaying or reversing a vast range of age-related diseases5. As cells of the immune system are responsible for senescent cell elimination6-11, a possible anti-aging and pro-healthspan treatment is the specific activation of the immune system to induce senescent cell clearance. However, whether this elimination is limited by an immune checkpoint leading to tolerance of senescence cells is currently unknown. Here, we show that cellular senescence, elicited by various stressors other than oncogenic activation, triggers immune escape toward natural killer (NK) cells, which may thus limit the use of anti-senescence immunotherapies. Moreover, using mass spectrometry, we reveal that senescent cells reshuffle their glycosphingosine composition, toward a marked increase in the ganglioside content, including the appearance of disialylated ganglioside GD3. This senescence associated GD3 overexpression results from transcriptional upregulation of the gene encoding the enzyme ST8SIA1, which is responsible for GD3 synthesis. The high level of GD3 leads to a strong immunosuppressive signal affecting NK cell-mediated immunosurveillance. In a mouse model of lung fibrosis, senescent cell-dependent NK cell immunosuppression is blunted by in vivo administration of anti-GD3 monoclonal antibodies leading to a clear anti-fibrotic effect. These results demonstrate that GD3 upregulation in senescent cells drives a switch from immune clearance toward immune tolerance of senescent cells. Therefore, we propose that GD3 level acts as a senescence-associated immune checkpoint (SIC) that regulates NK cell functions toward senescent cells. Thus, targeting GD3 with specific antibodies may be a promising strategy for the development of effective anti-senescence immunotherapies.

immunology↗

bioRxiv2017

The differential spatiotemporal expression pattern of shelterin genes throughout lifespan

Shelterin forms the core complex of telomere proteins and plays critical roles in protecting telomeres against unwanted activation of the DNA damage response and in maintaining telomere length homeostasis. Although shelterin expression is believed to be ubiquitous for stabilization of chromosomal ends, some evidence suggests that some shelterin subunits have tissue-specific functions. However, very little is known regarding how shelterin subunit gene expression is regulated during development and aging. Using two different animal models, the mouse and zebrafish, we reveal herein that shelterin subunits exhibit distinct spatial and temporal expression patterns that do not correlate with the proliferative status of the organ systems examined. Together, this work shows that the shelterin subunits exhibit distinct spatiotemporal expression patterns, suggesting important tissue-specific functions during development throughout the lifespan.

developmental biology↗