Biology subjects

Sadoughi, B.

Publications and source records attributed to Sadoughi, B..

5 recordsLinked to original sources

bioRxiv2026

Early-Life Wildfire Smoke Exposure Is Associated with Long-Term Systemic Immune Remodeling and Epigenetic Reprogramming

Wildfire smoke is an escalating global public health threat exposing millions of people, including children, to hazardous air pollution each year. Although wildfire smoke toxicants have been linked to a range of adverse health outcomes, including immune dysregulation, the long-term consequences of real-world pediatric wildfire smoke exposure on health and development remain largely unknown. To investigate the persistent effects of early-life exposure on immune health, here we leveraged a cohort of rhesus macaques that experienced nine consecutive days of hazardous wildfire smoke exposure in infancy during the 2020 Oregon Labor Day wildfires. By integrating ex vivo immune stimulations, multiplex cytokine profiling, single-cell transcriptomics, and genome-wide DNA methylation profiling, we identified persistent immunological consequences across molecular and functional levels. We found that a single severe postnatal exposure, in the first three months of life, was associated with persistent change in the innate immune response, including reduced pro-inflammatory cytokine response to a bacterial endotoxin, with subtle but consistent transcriptional changes in myeloid cells, particularly among males. Wildfire smoke exposure was also associated with changes in proportion of B and T/NK cells, and within the T/NK cell compartment, exposed animals exhibited an expansion of cytotoxic cells. Consistent with this, CD8+ T cells displayed extensive transcriptional remodeling and shifted toward more differentiated effector states, with the greatest differentiation observed in animals exposed at the youngest ages. Genome-wide DNA methylation profiling identified smoke-associated methylation changes consistent with acceleration of epigenetic aging, as well as persistent epigenetic alterations impacting genes involved in oxidative stress responses, innate immunity, T cell differentiation, and hematopoiesis. These findings demonstrate that a single severe wildfire smoke exposure during a critical developmental window is associated with extensive immune and epigenetic remodeling that persist years after exposure, providing new insight into the long-term biological consequences of early-life wildfire smoke exposure.

immunology↗

bioRxiv2025

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques

Age and early life adversity (ELA) are both key determinants of health, but whether they target similar physiological mechanisms across the body is unknown due to limited multi-tissue datasets from well-characterized cohorts. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free ranging rhesus macaques, with records of naturally occurring ELA. We show that age-associated DNAm variation is predominantly tissue-dependent, yet tissue-specific epigenetic clocks reveal that the pace of epigenetic aging is relatively consistent within individuals. ELA effects on loci are adversity-dependent, but a given ELA has a coordinated impact across tissues. Finally, ELA targeted many of the same loci as age, but the direction of these effects varied, indicating that ELA does not uniformly contribute to accelerated age in the epigenome. ELA thus imprints a coordinated, tissue-spanning epigenetic signature that is both distinct from and intertwined with age-related change, advancing our understanding of how early environments sculpt the molecular foundations of aging and disease.

genomics↗

bioRxiv2025

Non-invasive measures of DNA methylation capture molecular aging in wild capuchin monkeys

Elucidating the socio-ecological factors that shape patterns of epigenetic modification in long-lived vertebrates is of broad interest to evolutionary biologists, geroscientists, and ecologists. However, aging research in wild populations is limited due to inability to measure cellular hallmarks of aging noninvasively. Here, we demonstrate that cellular DNA methylation (DNAm) profiles from fecal samples provide an accurate and reliable molecular clock in wild capuchin monkeys. Analysis of blood, feces, and urine samples from a closely related species shows that DNAm differentiates between species and different types of biological samples. We further find age-associated differences in DNAm relevant to cellular damage, inflammation, and senescence, consistent with hallmarks conserved across humans and other mammalian species, speaking to the comparative potential. By demonstrating that DNAm can be studied non-invasively in wild animals, our research opens new avenues in the study of modifiers of the pace of aging, and increases potential for cross-population and species comparisons.

genomics↗

bioRxiv2024

Cost-effective solutions for high-throughput enzymatic DNA methylation sequencing

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, geroscience, and medical genomics. While costs are decreasing, whole-genome DNA methylation profiling remains prohibitively expensive for most population-scale studies, creating a need for cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target a subset of the genome). Most common whole genome and reduced representation techniques rely on bisulfite conversion, which can damage DNA resulting in DNA loss and sequencing biases. Enzymatic methyl sequencing (EM-seq) was recently proposed to overcome these issues, but thorough benchmarking of EM-seq combined with cost-effective, reduced representation strategies has not yet been performed. To do so, we optimized Targeted Methylation Sequencing protocol (TMS)--which profiles [~]4 million CpG sites--for miniaturization, flexibility, and multispecies use at a cost of [~]$80. First, we tested modifications to increase throughput and reduce cost, including increasing multiplexing, decreasing DNA input, and using enzymatic rather than mechanical fragmentation to prepare DNA. Second, we compared our optimized TMS protocol to commonly used techniques, specifically the Infinium MethylationEPIC BeadChip (n=55 paired samples) and whole genome bisulfite sequencing (n=6 paired samples). In both cases, we found strong agreement between technologies (R{superscript 2} = 0.97 and 0.99, respectively). Third, we tested the optimized TMS protocol in three non-human primate species (rhesus macaques, geladas, and capuchins). We captured a high percentage (mean=77.1%) of targeted CpG sites and produced methylation level estimates that agreed with those generated from reduced representation bisulfite sequencing (R{superscript 2} = 0.98). Finally, we applied our protocol to profile age-associated DNA methylation variation in two subsistence-level populations--the Tsimane of lowland Bolivia and the Orang Asli of Peninsular Malaysia--and found age-methylation patterns that were strikingly similar to those reported in high income cohorts, despite known differences in age-health relationships between lifestyle contexts. Altogether, our optimized TMS protocol will enable cost-effective, population-scale studies of genome-wide DNA methylation levels across human and non-human primate species.

genomics↗

bioRxiv2020

Assessing the reliability of an automated method for measuring dominance hierarchy in nonhuman primates

Among animals societies, dominance is an important social factor that influences inter-individual relationships. However, assessing dominance hierarchy can be a time-consuming activity which is potentially impeded by environmental factors, difficulties in the recognition of animals, or through the disturbance of animals during data collection. Here we took advantage of novel devices, Machines for Automated Learning and Testing (MALT), designed primarily to study nonhuman primates cognition - to additionally measure the social structure of a primate group. When working on a MALT, an animal can be replaced by another; which could reflect an asymmetric dominance relationship (or could happen by chance). To assess the reliability of our automated method, we analysed a sample of the automated conflicts with video scoring and found that 75% of these replacements include genuine forms of social displacements. We thus first designed a data filtering procedure to exclude events that should not be taken into account when automatically assessing social hierarchies in monkeys. Then, we analysed months of daily use of MALT by 25 semi-free ranging Tonkean macaques (Macaca tonkeana) and found that dominance relationships inferred from these interactions strongly correlate with the ones derived from observations of spontaneous agonistic interactions collected during the same time period. We demonstrate that this method can be used to assess the evolution of individual social status, as well as group-wide hierarchical stability longitudinally with minimal research labour. Further, it facilitates a continuous assessment of dominance hierarchies, even during unpredictable environmental or challenging social events. Altogether, this study supports the use of MALT as a reliable tool to automatically and dynamically assess social status within groups of nonhuman primates, including juveniles.

animal behavior and cognition↗