Biology subjects

Laurent, A.

Publications and source records attributed to Laurent, A..

15 recordsLinked to original sources

bioRxiv2025

Salmonids reveal principles of regulatory evolution following autotetraploidization

Early vertebrate autotetraploidization events may have enabled major innovations by expanding the genetic material for functional diversification, yet their ancient timing obscures how genome doubling reshaped gene regulatory evolution. Salmonids provide a unique window to these mechanisms, because they experienced a comparatively recent autotetraploidization and are earlier in the rediploidization process - which creates new genes and regulatory elements during evolution. Here, using large-scale multiomics spanning embryonic and adult tissues in two salmonids, we investigate gene regulatory evolution following genome doubling and rediploidization, which we show is governed by developmental and tissue-specific context, with a period of maximal constraint at advanced stages of embryogenesis. This work advances understanding of vertebrate genome evolution, while providing an open resource supporting salmonid aquaculture and conservation.

evolutionary biology↗

bioRxiv2024

Predicting inbred parent synchrony at flowering for maize hybrid seed production by integrating crop growth model with whole genome prediction

One of the challenges of maize hybrid seed production is to ensure synchrony at flowering of the two inbred parents of a hybrid, which depends on the specific parental combination and environmental conditions of the production field. Maize flowering can be simulated using a mechanistic crop growth model that converts thermal time accumulation to leaf numbers based on inbred specific physiological parameter values. Heretofore, these inbred specific physiological parameters need to be measured or assigned based on prior knowledge. Here, we leverage genetic, environmental and management data to predict physiological parameters and simulate flowering phenotypes by using whole genome prediction methodology combined with a crop growth model (CGM-WGP) as part of in-field in-season inbred growth development. We use two estimation sets that differ in terms of management and weather information to test the robustness of our approach. As part of our findings, we demonstrate the importance of defining informative priors to generate biologically meaningful predictions of unobserved physiological parameters. Our CGM-WGP infrastructure is efficient at simulating flowering phenotypes. An important practical application of our method is the ability to recommend differential planting intervals for male and female maize inbreds used in commercial seed production fields to synchronize male and female flowering. Core ideasO_LISynchrony at flowering of maize inbred parents is crucial for optimal pollination and consequently seed yield. C_LIO_LIIntegrating WGP with CGM can accurately predict physiological parameters and simulate maize flowering phenotypes. C_LIO_LICGM-WGP infrastructure can be used to optimize field operations for large scale maize hybrid seed production. C_LI

physiology↗

bioRxiv2024

A Toolbox for Neisseria meningitidis: Gene Editing, Complementation and Labelling

The efficient transformation of Neisseria meningitidis and Neisseria gonorrhoeae facilitates the rapid construction of bacterial mutants with insertion of antibiotic resistance cassettes. However, this strategy limits the construction of strains with multiple mutations. Recent advances in markerless strategies for Neisseria species have enabled the construction of mutants without antibiotic resistance markers. However, these innovative approaches have potential limitations related to the selection strategy or the possible occurrence of spontaneous mutations in the selection marker genes. In addition, complementation tools or labelling strategies for N. meningitidis are also lacking. In this study, we have introduced new tools for markerless mutation, genetic complementation and labelling in N. meningitidis, thus improving the research possibilities for understanding and tackling these pathogens.

microbiology↗

bioRxiv2024

PRDM9 drives the location and rapid evolution of recombination hotspots in salmonids

In many eukaryotes, meiotic recombination occurs preferentially at discrete sites, called recombination hotspots. In various lineages, recombination hotspots are located in regions with promoter-like features and are evolutionarily stable. Conversely, in some mammals, hotspots are driven by PRDM9 that targets recombination away from promoters. Paradoxically, PRDM9 induces the self-destruction of its targets and this triggers an ultra-fast evolution of mammalian hotspots. PRDM9 is ancestral to all animals, suggesting a critical importance for the meiotic program, but has been lost in many lineages with surprisingly little effect on meiosis success. However, it is unclear whether the function of PRDM9 described in mammals is shared by other species. To investigate this, we analyzed the recombination landscape of several salmonids, the genome of which harbors one full-length PRDM9 and several truncated paralogs. We identified recombination initiation sites in Oncorhynchus mykiss by mapping meiotic DNA double-strand breaks (DSBs). We found that DNA DSBs clustered at hotspots positioned away from promoters, enriched for the H3K4me3 and H3K4me36 marks and the location of which depended on the genotype of full-length Prdm9. We observed a high level of polymorphism in the zinc finger domain of full-length Prdm9, but not of the truncated paralogs. Moreover, population-scaled recombination maps in O. mykiss, Oncorhynchus kisutch and Salmo salar revealed a rapid turnover of recombination hotspots caused by PRDM9 target motif erosion. Our results imply that PRDM9 function is conserved across vertebrates and that the peculiar evolutionary runaway caused by PRDM9 has been active for several hundred million years.

evolutionary biology↗

bioRxiv2023

GET: a foundation model of transcription across human cell types

Transcriptional regulation, involving the complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate in unseen cell types and conditions. Here, we introduce GET, an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types. Relying exclusively on chromatin accessibility data and sequence information, GET achieves experimental-level accuracy in predicting gene expression even in previously unseen cell types. GET showcases remarkable adaptability across new sequencing platforms and assays, enabling regulatory inference across a broad range of cell types and conditions, and uncovering universal and cell type specific transcription factor interaction networks. We evaluated its performance on prediction of regulatory activity, inference of regulatory elements and regulators, and identification of physical interactions between transcription factors. Specifically, we show GET outperforms current models in predicting lentivirus-based massive parallel reporter assay readout with reduced input data. In fetal erythroblasts, we identify distal (>1Mbp) regulatory regions that were missed by previous models. In B cells, we identified a lymphocyte-specific transcription factor-transcription factor interaction that explains the functional significance of a leukemia-risk predisposing germline mutation. In sum, we provide a generalizable and accurate model for transcription together with catalogs of gene regulation and transcription factor interactions, all with cell type specificity.

bioinformatics↗

bioRxiv2023

Cryopreservation effect on DNA methylation profile in rainbow trout spermatozoa

Spermatozoa are the cells the most commonly used for cryopreservation of valuable genetic resources in aquaculture. It is known that fish spermatozoa transmit to the embryo not only their genetic but also their epigenetic profile, particularly DNA methylation. Therefore, any alteration of the DNA methylation profile in spermatozoa induces the risk of transmitting epigenetic alterations to the offspring. The aim of this study was to assess the effect of cryopreservation on DNA methylation in rainbow trout spermatozoa. To trigger variable cellular response after freezing-thawing, spermatozoa from mature males were cryopreserved with dimethyl sulfoxide, methanol or glycerol as cryoprotectant. We observed that dimethyl sulfoxide was the best to preserve thawed spermatozoa functions. Methanol preserved only slightly all the cellular parameters, while glycerol failed to protect motility and fertilization ability. The consequences on DNA methylation were assessed using Reduced Representation Bisulfite Sequencing (RRBS). Sperm cryopreservation did not thoroughly impact DNA methylation, although 335 to 564 differentially methylated cytosines were characterized depending on the cryoprotectant. Very few of them were shared between cryoprotectants, and no correlation with the extent of cellular damage was found. Our study showed that DNA methylation was only slightly altered after sperm cryopreservation, and this may render further analysis of the risk for the progeny very challenging.

cell biology↗

bioRxiv2023

Analysis of DNA methylation in rainbow trout spermatozoa: the strengths and limitations of RRBS

DNA methylation is an important epigenetic mark in fish spermatozoa since it has been shown that some sperm methylome features are transmitted to the offspring. To ensure the transmission of unaltered information to the offspring, the characterization of this mark and its stability in spermatozoa is essential. DNA methylation status can be assessed at the whole genome level with an identification of the methylated and unmethylated cytosines using RRBS (reduced representation bisulfite sequencing). This method allows the sequencing of a subset of the genome expected to be enriched in CpGs. We aim to characterize the data provided by RRBS in rainbow trout spermatozoa, in order to evaluate the suitability of this approach for sperm biotechnologies studies. We observed that RRBS did provide a reduced amount of genomic data, thus allowing the processing of many biological replicates. Although, in our dataset, only a small fraction of the whole genome CpGs was present in all 6 to 12 replicates, the sum of the analyzed CpGs spanned 9 % of the total genomic CpGs. They distributed evenly all over the genome, and all genomic features were represented. RRBS is therefore an effective method to scan the DNA methylation of the along genome in a reduced pattern. However, one should be aware of the choices that are to be made regarding fragment size selection and regarding the options during bioinformatic data processing.

molecular biology↗

bioRxiv2022

EPIGENETIC LANDSCAPE OF HEAT STRESS INTERGENERATIONAL INHERITANCE IN A TELEOST FISH

Epigenetic information is transmitted from cell to cell, and even generation to generation. The question of epigenetic inheritance in fish has become of crucial interest in the recent years, when the mammalian model of methylome erasure in germ cells and embryos was found not to be conserved. Fish, which are particularly exposed to environmental variations might thus be prone to transmit epigenetic alterations to their offspring, driving rapid environmental acclimation. Here, by sequencing spermatozoa and muscle methylomes, we characterized the methylation landscape of paternal gametes in rainbow trout and demonstrated its sensitivity to a 4{degrees}C increased rearing temperature during spermatogenesis. We found that spermatozoa methylome primes housekeeping and developmental genes for activation and might be instrumental to early development. Most of these methylation-free promoters were not affected by temperature, attesting the robustness of the epigenetic programming of early development. However, the increase of temperature triggered the differential methylation of 5,359 regions, among which 560 gene promoters control spermiogenesis and lipid metabolism. We therefore report, for the first time in fish, that sperm epigenetic landscape carries marks of parental environmental conditions. In the context of a 4{degrees}C temperature increase during spermatogenesis, we describe how rainbow trout sperm DNA methylation might be a molecular basis of intergenerational inheritance and question its role in controlling next generations performances and acclimation to climate change.

genomics↗

bioRxiv2021

TET2-mediated epigenetic reprogramming of breast cancer cells impairs lysosome biogenesis

Methylation and demethylation of cytosines in DNA are believed to act as keystones of cell-specific gene expression through controlling chromatin structure and accessibility to transcription factors. Cancer cells have their own transcriptional programs and we sought to alter such a cancer-specific program by enforcing expression of the catalytic domain (CD) of the methylcytosine dioxygenase TET2 in breast cancer cells. TET2 CD decreased the tumorigenic potential of cancer cells through both activation and repression of a repertoire of genes that, interestingly, differed in part from the one observed upon treatment with the hypomethylating agent decitabine. In addition to promoting the establishment of an antiviral state, TET2 activated 5mC turnover at thousands of MYC binding motifs and down-regulated a panel of known MYC-repressed genes involved in lysosome biogenesis and function. Thus, an extensive cross-talk between TET2 and the oncogenic transcription factor MYC establishes a lysosomal storage disease-like state that contributes to an exacerbated sensitivity to autophagy inducers.

cancer biology↗

bioRxiv2021

Changes in regional white matter volumetry and microstructure during the post-adolescence period: a cross-sectional study of a cohort of 1,713 university students

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilised to study white matter changes during development and ageing. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18 to 26. We assessed the age and sex dependence, as well as hemispheric asymmetry of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterised by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. We also report a robust hemispheric asymmetry in both the volume and microstructural properties in many regions. These findings emphasise the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

neuroscience↗

bioRxiv2020

3D segmentation of perivascular spaces on T1-weighted 3 Tesla MR images with a convolutional autoencoder and a U-shaped neural network

We implemented a deep learning (DL) algorithm for the 3-dimensional segmentation of perivascular spaces (PVSs) in deep white matter (DWM) and basal ganglia (BG). This algorithm is based on an autoencoder and a U-shaped network (U-net), and was trained and tested using T1-weighted magnetic resonance imaging (MRI) data from a large database of 1,832 healthy young adults. An important feature of this approach is the ability to learn from relatively sparse data, which gives the present algorithm a major advantage over other DL algorithms. Here, we trained the algorithm with 40 T1-weighted MRI datasets in which all "visible" PVSs were manually annotated by an experienced operator. After learning, performance was assessed using another set of 10 MRI scans from the same database in which PVSs were also traced by the same operator and were checked by consensus with another experienced operator. The Sorensen-Dice coefficients for PVS voxel detection in DWM (resp. BG) were 0.51 (resp. 0.66), and 0.64 (resp. 0.71) for PVS cluster detection (volume threshold of 0.5 within a range of 0 to 1). Dice values above 0.90 could be reached for detecting PVSs larger than 10 mm3 and 0.95 for PVSs larger than 15 mm3. We then applied the trained algorithm to the rest of the database (1,782 individuals). The individual PVS load provided by the algorithm showed a high agreement with a semi-quantitative visual rating done by an independent expert rater, both for DWM and for BG. Finally, we applied the trained algorithm to an age-matched sample from another MRI database acquired using a different scanner. We obtained a very similar distribution of PVS load, demonstrating the interoperability of this algorithm.

neuroscience↗

bioRxiv2020

The MRi-Share database: brain imaging in a cross-sectional cohort of 1,870 university students

We report on MRi-Share, a multi-modal brain MRI database acquired in a unique sample of 1,870 young healthy adults, aged 18 to 35 years, while undergoing university-level education. MRi-Share contains structural (T1 and FLAIR), diffusion (multispectral), susceptibility weighted (SWI), and resting-state functional imaging modalities. Here, we described the contents of these different neuroimaging datasets and the processing pipelines used to derive brain phenotypes, as well as how quality control was assessed. In addition, we present preliminary results on associations of some of these brain image-derived phenotypes at the whole brain level with both age and sex, in the subsample of 1,722 individuals aged less than 26 years. We demonstrate that the post-adolescence period is characterized by changes in both structural and microstructural brain phenotypes. Grey matter cortical thickness, surface area and volume were found to decrease with age, while white matter volume shows increase. Diffusivity, either radial or axial, was found to robustly decrease with age whereas fractional anisotropy only slightly increased. As for the neurite orientation dispersion and densities, both were found to increase with age. The isotropic volume fraction also showed a slight increase with age. These preliminary findings emphasize the complexity of changes in brain structure and function occurring in this critical period at the interface of late maturation and early aging.

neuroscience↗

bioRxiv2019

Demography, genetic, and extinction process in a spatially structured population of lekking bird

Understanding the mechanisms underlying biological extinctions is a critical challenge for conservation biologists. Both deterministic (e.g. habitat loss, fragmentation) and stochastic (i.e. demographic stochasticity, Allee effect) demographic processes are involved in population decline. Simultaneously, a decrease of population size has far-reaching consequences for genetics of populations by increasing the risk of inbreeding and the effects of genetic drift, which together inevitably results in a loss of genetic diversity and a reduced effective population size (Ne). These genetic factors may retroactively affect vital rates (a phenomenon coined inbreeding depression), and therefore reduce population growth and accelerate the extinction process of small populations. To date, few studies have simultaneously examined the demographic and genetic mechanisms driving the extinction of wild populations, and have most of the time neglected the spatial structure of populations. In this study, we examined demographic and genetic factors involved in the extinction process of a spatially structured population of a lekking bird, the western capercaillie (Tetrao urogallus). To address this issue, we collected capture-recapture and genetic data over a 6-years period in Vosges mountains, France. Our study showed that the population of T. urogallus experienced a severe decline between 2010 and 2015. We did not detect any Allee effect on survival and recruitment. By contrast, individuals of both sexes dispersed to avoid small leks, suggesting a behavioral response to a mate finding Allee effect. In parallel to this demographic decline, the population showed a low genetic diversity and high inbreeding. In addition, the effective population sizes at both lek and population levels was low. Despite this, we did not detected evidence of inbreeding depression: neither survival nor recruitment were affected by individual inbreeding level. Our study underlines the benefit from combining demographic and genetic approaches to investigate processes that are involved in biological extinctions.

ecology↗

bioRxiv2019

Spatial density estimates of Eurasian lynx (Lynx lynx) in the French Jura and Vosges Mountains

Obtaining estimates of animal population density is a key step in providing sound conservation and management strategies for wildlife. For many large carnivores however, estimating density is difficult because these species are elusive and wide-ranging. Here, we focus on providing the first density estimates of the Eurasian lynx (Lynx lynx) in the French Jura and Vosges mountains. We sampled a total of 413 camera trapping sites (with 2 cameras per site) between January 2011 and April 2016 in seven study areas across seven counties of the French Jura and Vosges mountains. We obtained 592 lynx detections over 19,035 trap days in the Jura mountain and 0 detection over 6,804 trap days in the Vosges mountain. Based on coat patterns, we identified a total number of 92 unique individuals from photographs, including 16 females, 13 males and 63 individuals of unknown sex. Using spatial capture-recapture (SCR) models, we estimated abundance in the study areas between 5 (SE = 0.1) and 29 (0.2) lynx and density between 0.24 (SE = 0.02) and 0.91 (SE = 0.03) lynx per 100 km2. We also provide a comparison with non-spatial density estimates and discuss the expected discrepancies. Our study is yet another example of the advantage of combining SCR methods and non-invasive sampling techniques to estimate density for elusive and wide-ranging species, like large carnivores. While the estimated densities in the French Jura mountain are comparable to other lynx populations in Europe, the fact that we detected no lynx in the Vosges mountain is alarming. Connectivity should be encouraged between the French Jura mountain, the Vosges mountain and the Palatinate Forest in Germany where a reintroduction program is currently ongoing. Our density estimates will help in setting a baseline conservation status for the lynx population in France.

ecology↗

bioRxiv2019

Kin-dependent dispersal influences relatedness and genetic structuring in a lek system

Kin selection and dispersal play a critical role in the evolution of cooperative breeding systems. Limited dispersal dramatically increases relatedness in spatially structured populations (population viscosity), with the result that neighbours tend to be genealogical relatives. Yet the increase in neighbours performance through altruistic interaction may also result in habitat saturation and thus exacerbate local competition between kin. Our goal was to detect the footprint of kin selection and competition by examining the spatial structure of relatedness and by comparing non-effective and effective dispersal in a population of a lekking bird, Tetrao urogallus. For this purpose, we analysed capture-recapture and genetic data collected over a 6-year period on a spatially structured population of T. urogallus in France. Our findings revealed a strong spatial structure of relatedness in males. They also indicated that the population viscosity allowed male cooperation through two non-exclusive mechanisms. First, at their first lek attendance, males aggregate in a lek composed of relatives. Second, the distance corresponding to non-effective dispersal dramatically outweighed effective dispersal distance, which suggests that dispersers incur high post-settlement costs. These two mechanisms result in strong population genetic structuring in males. In females, our findings revealed a lower level of spatial structure of relatedness and genetic structure in respect to males. Additionally, non-effective dispersal and effective dispersal distances in females were highly similar, which suggests limited post-settlement costs. These results indicate that kin-dependent dispersal decisions and costs are factors driving the evolution of cooperative courtship and have a genetic footprint in wild populations.

ecology↗