Biology subjects

Lalancette, C.

Publications and source records attributed to Lalancette, C..

8 recordsLinked to original sources

bioRxiv2026

Epigenetic Resilience to Early-Life Maternal Loss in African Savanna Elephants

Early-life trauma in humans, including maternal loss, is strongly associated with increased risk of chronic diseases, reduced life expectancy, and accelerated biological aging, as measured through epigenetic modifications, such as DNA methylation. Whether similar patterns occur in other long-lived, socially complex non-primate species, however, remains unknown. Elephants share key life-history traits with humans, including longevity, strong social bonds, and advanced cognitive abilities. Yet wild elephant populations face significant anthropogenic and environmental pressures, including poaching, habitat loss, and human-wildlife conflict that can result in maternal mortality and subsequent calf orphaning. We examined whether orphaning of elephant calves was associated with accelerated DNA methylation age and distinct epigenetic signatures. Contrary to our hypothesis and patterns observed in other species, orphaned African savanna elephants exhibited a younger DNA methylation age than non-orphans, no accelerated aging, and only limited differential methylation at CpG sites. At the genome-wide level, chronological age was not associated with differential CpG methylation after correcting for multiple testing. One interpretation of these findings is that elephants may have evolved mechanisms that buffer against epigenetic instability following stressful events. Investigating these protective mechanisms in elephants could inform strategies to mitigate the long-term health impacts of early-life trauma in humans. Significance StatementIn most mammals, early-life adversity, including maternal loss is associated with shorter lifespans and widespread epigenetic alterations. In contrast, we found that orphaned African savanna elephants exhibited a younger epigenetic age compared to non-orphans and showed only a weak distinct epigenetic signature. This unexpected pattern may reflect environmental influences, such as living under human care, or evolutionary adaptations that buffer against epigenetic instability. If the latter is confirmed, such mechanisms could confer resilience to the epigenetic consequences of early-life adversity.

genomics↗

bioRxiv2025

Comprehensive Transcriptomic and Epigenomic Insights into Environmental Toxicant Exposures: The TaRGET II Resource

Environmental exposures to toxic chemicals can profoundly alter the transcriptome and epigenome in both humans and animals, contributing to disease development across the lifespan. To elucidate how early-life exposure to toxicants exerts such persistent effects, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 2,564 epigenomes and 1,043 transcriptomes from longitudinal studies in mice. All data are publicly available through the TaRGET II data portal and the WashU Epigenome Browser. This resource from target (liver, brain, lung, heart) and surrogate (blood) tissues at weaning (3 weeks) and two adult time-points (5 and 10 months) characterized the molecular response to arsenic (As), lead (Pb), bisphenol-A (BPA), di-2-ethylhexyl phthalate(DEHP), tributyltin (TBT), tetrachlorodibenzo-p-dioxin (TCDD), and particulate matter with a diameter of <2.5m (PM2.5). The findings revealed persistent, toxicant-specific, sex-dependent epigenomic and transcriptomic perturbations, resulting in disrupted expression of 14,908 genes, altered chromatin accessibility at 87,409 regulatory elements, DNA methylation changes at 113,186 genomic regions, and chromatin state switching of histone modifications. The resulting high-resolution map of how environmental exposures reprogram the epigenome and transcriptome is broadly accessible via ToxiTaRGET database, offering unparalleled opportunities for the scientific community to investigate the molecular underpinnings of environmental toxicant exposures and their contributions to disease pathogenesis.

pharmacology and toxicology↗

bioRxiv2023

Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver Identifies Tissue- and Sex-Specific Changes with Implications for Genetic Imprinting

BackgroundMaternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications. ObjectiveWe examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2-ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver. MethodsFemale mice were exposed to human relevant doses of either Pb (32ppm) via drinking water or DEHP (5 mg/kg-day) via chow for two weeks prior to mating through offspring weaning. Whole genome bisulfite sequencing (WGBS) was utilized to examine DNAm changes in offspring cortex, blood, and liver at 5 months of age. Metilene and methylSig were used to identify differentially methylated regions (DMRs). Annotatr and Chipenrich were used for genomic annotations and geneset enrichment tests of DMRs, respectively. ResultsThe cortex contained the majority of DMRs associated with Pb (69%) and DEHP (58%) exposure. The cortex also contained the greatest degree of overlap in DMR signatures between sexes (n = 17 and 14 DMRs with Pb and DEHP exposure, respectively) and exposure types (n = 79 and 47 DMRs in males and females, respectively). In all tissues, detected DMRs were preferentially found at genomic regions associated with gene expression regulation (e.g., CpG islands and shores, 5 UTRs, promoters, and exons). An analysis of GO terms associated with DMR-containing genes identified imprinted genes to be impacted by both Pb and DEHP exposure. Of these, Gnas and Grb10 contained DMRs across tissues, sexes, and exposures. DMRs were enriched in the imprinting control regions (ICRs) of Gnas and Grb10, with 15 and 17 ICR-located DMRs across cortex, blood, and liver in each gene, respectively. The ICRs were also the location of DMRs replicated across target and surrogate tissues, suggesting epigenetic changes these regions may be potentially viable biomarkers. ConclusionsWe observed Pb- and DEHP-specific DNAm changes in cortex, blood, and liver, and the greatest degree of overlap in DMR signatures was seen between exposures followed by sex and tissue type. DNAm at imprinted control regions was altered by both Pb and DEHP, highlighting the susceptibility of genomic imprinting to these exposures during the perinatal window of development.

pharmacology and toxicology↗

bioRxiv2020

The SEQC2 Epigenomics Quality Control (EpiQC) Study: Comprehensive Characterization of Epigenetic Methods, Reproducibility, and Quantification

Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and a global resource for epigenetics research from the FDAs Epigenomics Quality Control (EpiQC) Group. The study design leverages seven human cell lines that are designated as reference materials and publicly available from the National Institute of Standards and Technology (NIST) and Genome in a Bottle (GIAB) consortium. These samples were subject to a variety of genome-wide methylation interrogation approaches across six independent laboratories, with a primary focus was on 5-methylcytosine modifications. Each sample was processed in two or more technical replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), one enzymatic deamination method (EMseq), targeted methylation sequencing (Illumina Methyl Capture EPIC), and single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, BWAMeth, and GemBS), we found overall high concordance between assays (R=0.87-R0.93), differences in efficency of read mapping and CpG capture and coverage, and platform performance. The data provided herein can guide continued used of these reference materials in epigenomics assays, as well as provide best practices for epigenomics research and experimental design in future studies.

genomics↗

bioRxiv2020

Associations of early social experience with offspring DNA methylation and later life stress phenotype

In a wild population of spotted hyenas, we tested the hypothesis that maternal care during the first year of life and social connectedness during two periods of early development lead to differences in DNA methylation and fecal glucocorticoid metabolites (fGCMs) later in life. We found that although maternal care and social connectedness during the communal den dependent period were not associated with fGCMs, greater social connectedness after hyenas leave their communal den is associated with lower adult fGCMs. Additionally, more maternal care and social connectedness after leaving the communal den corresponded with higher global (%CCGG) DNA methylation. Finally, we identified multiple DNA methylation biomarkers near genes involved in inflammation that may link maternal care and stress phenotype. Our findings suggest that both maternal care during the first year of life and social connections after leaving the den influence DNA methylation and contribute to a developmentally plastic stress response.

animal behavior and cognition↗

bioRxiv2020

Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits

BackgroundSkeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases, mobility, and quality of life. It is composed of several different cell and muscle fiber types. ResultsHere, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell-specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 30,531 nuclei, representing 11 libraries, profiled in this study, and identify seven distinct cell types ranging in abundance from 63% (type II fibers) to 0.9% (muscle satellite cells) of all nuclei. We introduce a regression-based approach to infer cell types by comparing transcription start site-distal ATAC-seq peaks to reference enhancer maps and show consistency with RNA-based marker gene cell type assignments. We find heterogeneity in enrichment of genetic variants linked to complex phenotypes from the UK Biobank and diabetes genome wide association studies in cell-specific ATAC-seq peaks, with the most striking enrichment patterns in muscle mesenchymal stem cells ([~]3% of nuclei). Finally, we overlay these chromatin accessibility maps on GWAS data to nominate causal cell types, SNPs, and transcription factor motifs for creatinine levels and type 2 diabetes signals. ConclusionsThese chromatin accessibility profiles for human and rat skeletal muscle cell types are a useful resource for investigating specific cell types and nominating causal GWAS SNPs and cell types.

genomics↗

bioRxiv2020

Local adaptation of Legionella pneumophila within a hospital hot water system increases tolerance to copper

In large-building water systems, Legionella pneumophila is exposed to common environmental stressors such as copper. The aim of this study was to evaluate the susceptibility to copper of L. pneumophila isolates recovered from various sites: two clinical and seven environmental from hot water systems biofilm & water, and from cooling tower water. After one-week acclimation in simulated drinking water, strains were exposed to various copper concentrations (0.8 to 5 mg/L) for over 672 hours. Complete loss of culturability was observed for three isolates, following copper exposure to 5 mg/L for 672h. Two ST1427-like isolates were highly sensitive to copper, while the other two, isolated from biofilm samples, were resistant. The expression of the copper resistance gene copA evaluated by RT-qPCR was significantly higher for the biofilm isolates. All four ST1427-like isolates were recovered from the same water system during an outbreak. Whole genome sequencing results confirmed that the four isolates are very close phylogenetically, differing by only 29 single nucleotide polymorphisms, suggesting in situ adaptation to microenvironmental conditions, possibly due to epigenetic regulation. These results indicate that the immediate environment within a building water distribution system influences the tolerance of L. pneumophila to copper. Increased contact of L. pneumophila biofilm strains with copper piping or copper alloys in the heat exchanger might lead to local adaptation. The phenotypic differences observed between water and biofilm isolates from the hot water system of a healthcare facility warrants further investigation to assess the relevance of evaluating disinfection performances based on water sampling alone. ImportanceLegionella pneumophila is a pathogen indigenous to natural and large building water systems in the bulk and the biofilm phases. The immediate environment within a system can impact the tolerance of L. pneumophila to environmental stressors, including copper. In healthcare facilities, copper levels in water can vary, depending on water quality, plumbing materials and age. This study evaluated the impact of the isolation site (water vs biofilm, hot water system vs cooling tower) within building water systems. Closely related strains isolated from a healthcare facility hot water system exhibited variable tolerance to copper stress shown by differential expression of copA, with biofilm isolates displaying highest expression and tolerance. Relying on the detection of L. pneumophila in water samples following exposure to environmental stressor such as copper may underestimate the prevalence of L. pneumophila, leading to inappropriate risk management strategies and increasing the risk of exposure for vulnerable patients.

microbiology↗

bioRxiv2019

Perinatal exposure to lead results in altered DNA methylation in adult mouse liver and blood: Implications for target versus surrogate tissue use in environmental epigenetics

BackgroundDNA methylation is a critical epigenetic mechanism linking early developmental environment to long-term health. In humans, the extent to which toxicant-induced changes in DNA methylation in surrogate tissues, such as blood, mirror those in the target tissues is unclear. The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET II) consortium was established by the National Institute of Environmental Health Sciences to address the utility of surrogate tissues as proxies for toxicant-induced epigenetic changes in target tissues.\n\nObjectivesThe objective of this study was to investigate the effects of perinatal exposure to a human environmentally relevant level (32 ppm in maternal drinking water) of lead (Pb) on liver and blood DNA methylation in adult male and female mice. We hypothesized that developmental Pb exposure would lead to persistent changes in DNA methylation, and that a subset of differentially methylated loci would overlap between liver and blood.\n\nMethodsEnhanced reduced-representation bisulfite sequencing was used to assess DNA methylation in 5 month old Pb-exposed and control mice. Sex-stratified modeling of differential methylation by Pb exposure was conducted using an established bioinformatics pipeline.\n\nResultsAlthough Pb exposure ceased at 3 weeks of age, we observed thousands of stably modified, sex-specific differentially methylated regions in the blood and liver of Pb-exposed animals, including 44 genomically imprinted loci. In males, we discovered 5 sites that overlapped between blood and liver, and exhibited changes in DNA methylation in the same direction in both tissues.\n\nConclusionsThese data demonstrate that perinatal exposure to Pb induces sex-specific changes in hepatic DNA methylation in adulthood, some of which are also present in blood. Ongoing studies will provide additional exposure-specific insights, and include other epigenetic marks that will enable further refinement of the design and analysis of human studies where target tissues are inaccessible.

genomics↗