Biology subjects

Milciute, M.

Publications and source records attributed to Milciute, M..

4 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

Whole-genome DNA methylation profiling in COVID-19 positive patients reveals alterations in pathways linked to neurological dysfunction

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible RNA betacoronavirus, causing coronavirus disease-19 (COVID-19). Infection with SARS-CoV-2 can result in a broad spectrum of clinical outcomes, ranging from asymptomatic or mild to a severe, deadly illness. Emerging evidence suggests SARS-CoV-2 affects host gene regulation through epigenetic mechanisms, such as DNA methylation, potentially contributing to immune dysregulation and post-acute sequelae, including neurological and psychiatric disorders. However, the extent and functional relevance of these epigenetic changes remain uncertain. Methods and resultsWe employed whole-genome bisulfite sequencing to profile DNA methylation in peripheral blood from SARS-CoV-2-positive patients across a spectrum of symptom severity, ranging from asymptomatic to severe (n=101), in comparison to SARS-CoV-2-negative individuals (n=105). We observed a widespread hypomethylation in the genomes of infected individuals, which was more pronounced in severe cases. Notably, we identified differentially methylated genes in patients with mild (19 genes), moderate (19 genes), and severe (35 genes) symptoms. These genes included those involved in canonical immune responses as well as known to be linked to neurodegenerative diseases. Subsequent pathway enrichment analysis further supported the significant association between the differentially methylated genes and those implicated in Alzheimers and Parkinsons disease, as well as neuropsychiatric conditions, suggesting potential epigenetic links between acute SARS-CoV-2 infection and long-term neurological outcomes. This is one of the first studies to comprehensively map severity-stratified genome-wide DNA methylation changes in COVID-19 patients. ConclusionOur findings underscore the potential importance of epigenetic regulation in the acute responses to SARS-CoV-2 infection and highlight an overlap with epigenetic mechanisms relevant for neuropsychiatric disease processes.

neuroscience↗

bioRxiv2024

Tet2 loss suppress α-synuclein pathology by stimulating ciliogenesis

There are no approved treatments that slow Parkinsons disease (PD) progression and therefore it is important to identify novel pathogenic mechanisms that can be targeted. Loss of the epigenetic marker, Tet2 appears to have some beneficial effects in PD models, but the underlying mechanism of action is not well understood. We performed an unbiased transcriptomic analysis of cortical neurons isolated from patients with PD to identify dysregulated pathways and determine their potential contributions to the disease process. We discovered that genes associated with primary cilia, non-synaptic sensory and signaling organelles, are upregulated in both early and late PD patients. Enhancing ciliogenesis in primary cortical neurons via sonic hedgehog signaling suppressed the accumulation of -synuclein pathology in vitro. Interestingly, deletion of Tet2 in mice also enhanced the expression of primary cilia and sonic hedgehog signaling genes and rescued the accumulation of -synuclein pathology and dopamine neuron degeneration in vivo. Our findings demonstrate the crucial role of Tet2 loss in regulating ciliogenesis and potentially affecting the progression of PD pathology.

neuroscience↗

bioRxiv2023

Human Endogenous Retrovirus Expression is Dynamically Regulated in Parkinson's Disease

Parkinsons disease (PD) is a progressive, debilitating neurodegenerative disease that afflicts approximately every 1000th individual. Recently, activation of genomic transposable elements (TE) has been suggested as a potential driver of PD onset. However, it is unclear where, when, and to what extent TEs are dysregulated in PD. Here, we performed a multi-tissue transcriptional analysis of multiple patient cohorts and identified TE transcriptional activation as a hallmark of PD. We find that PD patients exhibit up-regulation primarily of human endogenous retrovirus (HERV) transcripts in prefrontal cortex tissue, prefrontal neurons as well as in blood, and we demonstrate that TE activation in the blood is highest at the time of PD diagnosis. Supporting a potentially causal association between ERV dysregulation and PD heterogeneity, reduced gene dosage of the TE repressor Trim28 triggers transcriptional changes highly correlated to those measured in animal models of synucleinopathy (PFF-injection), and importantly, to those exhibited by patients themselves. These data identify ERV up-regulation as a common feature of central and peripheral PD etiology, and highlight potential roles for Trim28-dependent TEs in stratifying and monitoring PD and treatment compliance.

neuroscience↗