An improved epigenetic counter to track mitotic age in normal and precancerous tissues DOI Creative Commons
Tianyu Zhu, Huige Tong,

Zhaozhen Du

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 29, 2023

Abstract The cumulative number of stem cell divisions in a tissue, known as mitotic age, is thought to be major determinant cancer-risk. Somatic mutational and DNA methylation (DNAm) clocks are promising tools molecularly track yet their relationship underexplored potential for cancer risk prediction normal tissues remains demonstrated. Here we build validate an improved pan-tissue DNAm counter total age called stemTOC. We demonstrate that stemTOC’s proxy increases with the tumor cell-of-origin fraction each 15 cancer-types, precancerous lesions, exposed factors. Extensive benchmarking against 6 other counters shows stemTOC compares favorably, specially preinvasive normal-tissue contexts. By cross-correlating two clock-like somatic signatures, confirm mitotic-like nature only one these. Our data points towards molecular substrate detecting mitotic-age hence developing cancer-risk strategies.

Language: Английский

Epigenetics of prenatal stress in humans: the current research landscape DOI Creative Commons
Linda Dieckmann, Darina Czamara

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 2, 2024

Abstract Fetal exposure to prenatal stress can have significant consequences on short- and long-term health. Epigenetic mechanisms, especially DNA methylation (DNAm), are a possible process how these adverse environmental events could be biologically embedded. We evaluated candidate gene as well epigenome-wide association studies associating DNAm changes in peripheral tissues; however, most of findings lack robust replication. Prenatal stress-associated epigenetic also been linked child health including internalizing problems, neurobehavioral outcomes reactivity. Future should focus refined measurement definition its timing, ideally incorporating genomic longitudinal information. This will provide further opportunities enhance our understanding the biological embedding exposure.

Language: Английский

Citations

14
An improved epigenetic counter to track mitotic age in normal and precancerous tissues DOI Creative Commons
Tianyu Zhu, Huige Tong,

Zhaozhen Du

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 17, 2024

Abstract The cumulative number of stem cell divisions in a tissue, known as mitotic age, is thought to be major determinant cancer-risk. Somatic mutational and DNA methylation (DNAm) clocks are promising tools molecularly track yet their relationship underexplored potential for cancer risk prediction normal tissues remains demonstrated. Here we build validate an improved pan-tissue DNAm counter total age called stemTOC. We demonstrate that stemTOC’s proxy increases with the tumor cell-of-origin fraction each 15 cancer-types, precancerous lesions, exposed factors. Extensive benchmarking against 6 other counters shows stemTOC compares favorably, specially preinvasive normal-tissue contexts. By cross-correlating two clock-like somatic signatures, confirm mitotic-like nature only one these. Our data points towards molecular substrate detecting mitotic-age hence developing cancer-risk strategies.

Language: Английский

Citations

7
Assessing in-vitro models for microglial development and fetal programming: a critical review DOI Creative Commons
Steven Schepanski, Gonza Ngoumou, Claudia Buß

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

This review evaluates in-vitro models for studying how maternal influences during pregnancy impact the development of offspring microglia, immune cells central nervous system. The examined include primary microglia cultures, cell lines, iPSC-derived PBMC-induced microglia-like cells, 3D brain organoids derived from iPSCs, and Hofbauer cells. Each model is assessed its ability to replicate in-vivo environment developing brain, with a focus on their strengths, limitations, practical challenges. Key factors such as scalability, genetic epigenetic fidelity, physiological relevance are highlighted. Microglia lines highly scalable but lack fidelity. provide moderate patient-specific insights face operational challenges inherent reprogramming. organoids, offer an advanced platform complex neurodevelopmental processes require extensive resources technical expertise. which fetal macrophages located in placenta share common developmental origin uniquely exposed prenatal and, depending barrier maturation, exhibit variable makes them particularly useful exploring programming microglial development. concludes that no single comprehensively captures all aspects development, it offers guidance selecting most appropriate based specific research objectives experimental constraints.

Language: Английский

Citations

0
Genetic diversity of the immunoglobulin heavy chain locus in cohorts of patients affected with SARS-CoV-2 DOI Creative Commons
Patrizia Malaspina,

Carla Jodice,

Bianca Maria Ciminelli

et al.

Human Genomics, Journal Year: 2025, Volume and Issue: 19(1)

Published: Jan. 30, 2025

Language: Английский

Citations

0
Early life epigenetics and childhood outcomes: a scoping review DOI
Srirupa Hari Gopal, Theresa Alenghat, Mohan Pammi

et al.

Pediatric Research, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

Citations

2
Impact of Maternal SARS-CoV-2 Infection During Pregnancy on Offspring Neurodevelopment: Signature Cohort 12 Month Follow-Up. DOI Creative Commons
Nathalia Garrido-Torres,

Andrés Román-Jarrín,

J. Alfred Rider

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

Abstract The COVID-19 pandemic brought unprecedented global challenges. Amid the crisis, potential impact of SARS-CoV-2 on neurodevelopment offspring born to infected mothers emerged as a critical concern. This is prospective cohort study exposed maternal mild or severe infection during pregnancy. Pregnant women who acquired were enrolled in SIGNATURE project at Hospital Universitario Virgen del Rocio Seville, Spain, between 01/01/2021 and 08/31/2022. Maternal stress was assessed through Perceived Stress Scale; Ages & Stages Questionnaire, 3rd Edition (ASQ-3) 6 months 12 months. Association illness severity neurodevelopmental outcomes analyzed with univariate multivariate analysis. included 671 categorized into three distinct groups based severity: non-infected (N = 272), symptoms 346), 53). In utero exposure associated significant delay ASQ-3 personal-social subdomain follow-up [OR 3.00 (95% CI 1.129–7.969), p 0.028] independently timing stress. revealed association pregnancy 12-month follow-up, emphasizing importance understanding addressing long-term consequences neurodevelopment.

Language: Английский

Citations

0
Technical considerations for placental tissue processing and the subsequent impact on genome-wide DNA methylation analysis DOI Creative Commons
Kristen Kocher, Julius S. Ngwa, Kushal Kapse

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Sept. 16, 2024

To assess the impact of postnatal processing on placental DNA methylation, array data from flash-frozen tissue was compared to perfluorocarbon-immersed and formalin-fixed paraffin-embedded tissue. We observed that exposed perfluorocarbon showed no significant methylation differences when unprocessed tissue, while formalin altered quality reliability produced platform. Placental allows for study gene-environment interactions influence fetal environment development. Our highlights post-processing techniques must be considered in evaluation interpretation epigenetic studies.

Language: Английский

Citations

0
Maternal immune activation and autism in the offspring—what is the evidence for causation? DOI Creative Commons
Renee M. Gardner, Martin Brynge, Hugo Sjöqvist

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

0
Impact of Maternal Stress and COVID-19 Exposure During Pregnancy on Offspring Neurodevelopment: Signature Cohort 12 Month Follow-Up DOI Creative Commons
Nathalia Garrido-Torres,

Andrés Román-Jarrín,

J. Alfred Rider

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Abstract The COVID-19 pandemic brought unprecedented global challenges. Amid the crisis, potential impact of exposure on neurodevelopment offspring born to infected mothers emerged as a critical concern. This is prospective cohort study exposed mild or severe during pregnancy. Pregnant women who acquired SARS-CoV-2 were enrolled in SIGNATURE project at Hospital Universitario Virgen del Rocio Seville, Spain, between 01/01/2021 and 08/31/2022. Maternal stress was assessed through Perceived Stress Scale; screened Ages & Stages Questionnaire, 3rd Edition (ASQ-3) 6 months 12 months. Association severity neurodevelopmental outcomes analyzed with univariate multivariate analysis. included 689 categorized into three distinct groups based severity: non-infected (N = 277), 358), 54). In utero infection nearly tripled risk developmental concern ASQ-3 personal-social subdomain follow-up [OR 2.751 (95% CI 1.065–7.106), p 0.037], independently timing maternal stress. While this did not yield statistically significant results, it highlights need further investigate association pregnancy understand long-term consequences prenatal exposure.

Language: Английский

Citations

0
An improved epigenetic counter to track mitotic age in normal and precancerous tissues DOI Creative Commons
Tianyu Zhu, Huige Tong,

Zhaozhen Du

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 29, 2023

Abstract The cumulative number of stem cell divisions in a tissue, known as mitotic age, is thought to be major determinant cancer-risk. Somatic mutational and DNA methylation (DNAm) clocks are promising tools molecularly track yet their relationship underexplored potential for cancer risk prediction normal tissues remains demonstrated. Here we build validate an improved pan-tissue DNAm counter total age called stemTOC. We demonstrate that stemTOC’s proxy increases with the tumor cell-of-origin fraction each 15 cancer-types, precancerous lesions, exposed factors. Extensive benchmarking against 6 other counters shows stemTOC compares favorably, specially preinvasive normal-tissue contexts. By cross-correlating two clock-like somatic signatures, confirm mitotic-like nature only one these. Our data points towards molecular substrate detecting mitotic-age hence developing cancer-risk strategies.

Language: Английский

Citations

0