Transcriptomic characterization of 2D and 3D human induced pluripotent stem cell-based in vitro models as New Approach Methodologies for developmental neurotoxicity testing.

The safety and developmental neurotoxicity (DNT) potential of chemicals remain critically understudied due to limitations of current in vivo testing guidelines, which are low throughput, resource-intensive, and hindered by species differences that limit their relevance to human health. To address these issues, robust New Approach Methodologies (NAMs) using deeply characterized cell models are essential. This study presents the comprehensive transcriptomic characterization of two advanced human-induced pluripotent stem cell (hiPSC)-derived models: a 2D adherent and a 3D neurosphere model of human neural progenitor cells (hiNPCs) differentiated up to 21 days.

Blood miRNA levels associated with ADHD traits in children across six European birth cohorts.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance.

Dose rate dependent reduction in chromatin accessibility at transcriptional start sites long time after exposure to gamma radiation.

Ionizing radiation (IR) impact cellular and molecular processes that require chromatin remodelling relevant for cellular integrity. However, the cellular implications of ionizing radiation (IR) delivered per time unit (dose rate) are still debated. This study investigates whether the dose rate is relevant for inflicting changes to the epigenome, represented by chromatin accessibility, or whether it is the total dose that is decisive.

Transcriptional analysis in peripheral blood cells of individuals with elevated phthalate exposure - Results of the EuroMix study.

Exposure to phthalates is widespread in Europe. Phthalates are considered endocrine disrupting compounds and are classified as toxic for reproduction. However how phthalates affect the transcriptome in humans remains largely unknown.

Developmental neurotoxicity of acrylamide and its metabolite glycidamide in a human mixed culture of neurons and astrocytes undergoing differentiation in concentrations relevant for human exposure.

Neural stem cells (NSCs) derived from human induced pluripotent stem cells were used to investigate effects of exposure to the food contaminant acrylamide (AA) and its main metabolite glycidamide (GA) on key neurodevelopmental processes. Diet is an important source of human AA exposure for pregnant women, and AA is known to pass the placenta and the newborn may also be exposed through breast feeding after birth. The NSCs were exposed to AA and GA (1 ×10 - 3 ×10 M) under 7 days of proliferation and up to 28 days of differentiation towards a mixed culture of neurons and astrocytes.