A5032505274- Epigenetics and DNA Methylation
- Metabolomics and Mass Spectrometry Studies
- Genetic Associations and Epidemiology
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Bioinformatics and Genomic Networks
- Diet and metabolism studies
- Diabetes and associated disorders
- Chronic Disease Management Strategies
- Lipid metabolism and biosynthesis
- Pancreatic function and diabetes
- Diabetes Management and Education
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Genetic Syndromes and Imprinting
- Birth, Development, and Health
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Diabetes Management and Research
- Gene expression and cancer classification
- Neonatal Respiratory Health Research
- Clinical practice guidelines implementation
Leiden University Medical Center
2016-2025
Amsterdam University Medical Centers
2019-2024
Vrije Universiteit Amsterdam
2019-2024
Public Health Service of Amsterdam
2021-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2018-2023
Food & Nutrition
2023
Amsterdam Public Health
2020-2021
Leiden University
2017-2021
Amsterdam Neuroscience
2021
Oncode Institute
2020-2021
Abstract Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on genome-scale analysis differential whole blood after periconceptional exposure to famine during Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by...
Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and endothelial also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs MTs with CFs sarcomeric structures T-tubules, enhanced contractility, mitochondrial...
Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm whole blood mediated association prenatal famine exposure health 422 individuals exposed to utero 463 (sibling) controls. We implemented a two-step analysis, namely, genome-wide exploration across 342,596...
Abstract Background DNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due differences study design and focus there still is no consensus the annotation of regions predominantly involved tissue-specific methylation. We used new algorithm identify annotate differentially methylated (tDMRs) from Illumina 450k chip data for four peripheral (blood, saliva, buccal swabs...
Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that exposure elevated blood lipids prime circulating immune cells through changes in DNA methylation, process may contribute the development of atherosclerosis. To interrogate causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density (HDL) cholesterol levels genome-wide methylation while excluding confounding pleiotropy, we perform stepwise Mendelian...
Abstract Summary: The Illumina 450k array is a frequently used platform for large-scale genome-wide DNA methylation studies, i.e. epigenome-wide association studies. Currently, quality control of data can be performed with Illumina’s GenomeStudio and part limited number analysis pipelines. However, cannot handle existing pipelines provide options neither support interactive exploration by the user. To aid detection bad-quality samples in studies as flexible transparent possible, we have...
Background: The manipulation of pregnancy diets in animals can lead to changes DNA methylation with phenotypic consequences the offspring. Human studies have concentrated on effects nutrition during early gestation. Lacking humans is an epigenome-wide association study relation perturbations across all gestation periods. Methods: We used quasi-experimental setting Dutch famine 1944–45 evaluate impact exposure specific 10-week periods, or any time gestation, genome-wide levels at age ∼ 59...
The well-established association of chronological age with changes in DNA methylation is primarily founded on the analysis large sets blood samples, while conclusions regarding tissue-specificity are typically based small number tissues and CpGs. Here, we systematically investigate tissue-specific character age-related at level CpG, functional genomic region nearest gene a dataset.We assembled compendium public data, encompassing genome-wide data (Illumina 450k array) 8092 samples from 16...
Epigenetic change is a hallmark of ageing but its link to mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, changes relevant biological age are expected gradually dissociate from mirroring the increased heterogeneity health status older ages.Here, we report on large-scale identification 6366 age-related variably methylated positions (aVMPs) identified 3295 whole blood profiles, 2044 which have matching RNA-seq gene...
Abstract Human embryonic stem cells (hESCs) closely resemble mouse epiblast exhibiting primed pluripotency unlike ESCs (mESCs), which acquire a naïve pluripotent state. Efforts have been made to trigger in hESCs for subsequent unbiased lineage-specific differentiation, common conundrum faced by due heterogeneity gene expression existing within and between hESC lines. This required either ectopic of genes such as NANOG KLF2 or inclusion multiple pluripotency-associated factors. We report here...
Abstract Aims/hypothesis Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate cross-validate these in three large cohorts using variables readily measured clinic. Methods independent cohorts, total 15,940 individuals were clustered age, BMI, HbA 1c , random or fasting C-peptide, HDL-cholesterol. Clusters cross-validated against original HOMA measures. addition, between...
Abstract Background Epigenetic clocks use DNA methylation (DNAm) levels of specific sets CpG dinucleotides to accurately predict individual chronological age. A popular application these is explore whether the deviation predicted age from associated with disease phenotypes, where this interpreted as a potential biomarker biological This wide application, however, contrasts limited insight in processes that may drive running epigenetic clocks. Results We perform functional genomics analysis...
Abstract Aims/hypothesis The aim of this study was to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in whole blood people with type 2 diabetes across five different clusters: severe insulin-deficient (SIDD), insulin-resistant (SIRD), mild obesity-related (MOD), (MD) high HDL-cholesterol (MDH) . This increase our understanding molecular mechanisms underlying the putative clusters diabetes. Methods Participants Hoorn Diabetes Care System (DCS) cohort were clustered...
Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge DNA methylation dynamics in human tissue specification organ largely stems from extrapolation studies vitro animal models. Here, we report on landscape using 450k array four tissues (amnion, muscle, adrenal pancreas) during first second trimester gestation (9,18 22 weeks). We show that tissue-specific signature, constituted by hypomethylated CpG sites, was already present at...
Abstract Epigenetic remodeling is one of the major features aging process. We recently demonstrated that DNA methylation ELOVL2 and FHL2 CpG islands highly correlated with age in whole blood. Here we investigated several aspects age-associated hypermethylation FHL2. showed significantly different primary dermal fibroblast cultures from donors ages. Using epigenomic data public resources, most tissues show age. Interestingly, was not found very low replication rate. associated vitro cell...
EpiTYPER® is a mass spectrometry-based bisulfite sequencing method that enables region-specific DNA methylation analysis in quantitative and high-throughput fashion. The technology targets genomic regions of 100-600 base pairs results the measurement levels largely at single-nucleotide resolution. It particularly suitable for larger scale efforts to study candidate or validate from genome-wide studies. Here, we describe detail how design perform EpiTYPER measurements preprocess data,...
Preeclampsia (PE) carries increased risks of cardiovascular- and metabolic diseases in mothers offspring during the life course. While severe early-onset PE (EOPE) phenotype originates from impaired placentation early pregnancy, late-onset (LOPE) is particular associated with pre-existing maternal risk factors. We hypothesize that altered epigenetic programming placental fetal tissues these changes might elucidate disease susceptibility offspring.A nested case-control study was conducted The...
Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of previous study clustered people according to five subtypes. The aim the current investigate etiology these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were based on clinical characteristics. subset, genetic (N = 12,828), metabolomic 2,945), lipidomic 2,593), and proteomic 1,170) data obtained plasma....