scholarly journals Integrated RNA Sequencing Reveals Epigenetic Impacts of Diesel Particulate Matter Exposure in Human Cerebral Organoids

2020 ◽  
Vol 42 (5-6) ◽  
pp. 195-207
Author(s):  
Stephanie M Bilinovich ◽  
Katie L. Uhl ◽  
Kristy Lewis ◽  
Xavier Soehnlen ◽  
Michael Williams ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Brain Development ◽  
Single Cell ◽  
Developmental Disorders ◽  
Radial Glia ◽  
Autism Spectrum ◽  
Cellular Respiration ◽  
Diesel Particulate Matter ◽  
Diesel Particulate ◽  
Outer Radial Glia

Autism spectrum disorder (ASD) manifests early in childhood. While genetic variants increase risk for ASD, a growing body of literature has established that in utero chemical exposures also contribute to ASD risk. These chemicals include air-based pollutants like diesel particulate matter (DPM). A combination of single-cell and direct transcriptomics of DPM-exposed human-induced pluripotent stem cell-derived cerebral organoids revealed toxicogenomic effects of DPM exposure during fetal brain development. Direct transcriptomics, sequencing RNA bases via Nanopore, revealed that cerebral organoids contain extensive RNA modifications, with DPM-altering cytosine methylation in oxidative mitochondrial transcripts expressed in outer radial glia cells. Single-cell transcriptomics further confirmed an oxidative phosphorylation change in cell groups such as outer radial glia upon DPM exposure. This approach highlights how DPM exposure perturbs normal mitochondrial function and cellular respiration during early brain development, which may contribute to developmental disorders like ASD by altering neurodevelopment.

scholarly journals Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics

2020 ◽  
Vol 17 (20) ◽  
pp. 7386
Author(s):  
Stephanie M. Bilinovich ◽  
Kristy Lewis ◽  
Barbara L. Thompson ◽  
Jeremy W. Prokop ◽  
Daniel B. Campbell
Keyword(s):  
Particulate Matter ◽  
Environmental Factors ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Molecular Networks ◽  
Diesel Particulate Matter ◽  
Genome Wide Association Studies ◽  
Diesel Particulate ◽  
Genetic And Environmental Factors

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disruptions in social communication and behavioral flexibility. Both genetic and environmental factors contribute to ASD risk. Epidemiologic studies indicate that roadway vehicle exhaust and in utero exposure to diesel particulate matter (DPM) are associated with ASD. Using the Comparative Toxicogenomics Database (CTD), we identified genes connected to DPM exposure and ASD, extracted the known enhancers/promoters of the identified genes, and integrated this with Assay for Transposase Accessible Chromatin (ATAC-seq) data from DPM-exposed human neural progenitor cells. Enhancer/promoter elements with significantly different chromosome accessibility revealed enriched DNA sequence motifs with transcription factor binding sites for EGR1. Variant extraction for linkage disequilibrium blocks of these regions followed by analysis through Genome Wide Association Studies (GWAS) revealed multiple neurological trait associations including exploratory eye movement and brain volume measurement. This approach highlights the effects of pollution on the regulatory regions of genes implicated in ASD by genetic studies, indicating convergence of genetic and environmental factors on molecular networks that contribute to ASD. Integration of publicly available data from the CTD, cell culture exposure studies, and phenotypic genetics synergize extensive evidence of chemical exposures on gene regulation for altered brain development.

Scrubbing effect on diesel particulate matter from transesterified waste oils blends

Fuel ◽  
2006 ◽  
Vol 85 (7-8) ◽  
pp. 923-928 ◽  
Author(s):  
A. Durán ◽  
J.M. Monteagudo ◽  
O. Armas ◽  
J.J. Hernández
Keyword(s):  
Particulate Matter ◽  
Diesel Particulate Matter ◽  
Diesel Particulate ◽  
Waste Oils

scholarly journals Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

2021 ◽  
Author(s):  
Ugomma C. Eze ◽  
Aparna Bhaduri ◽  
Maximilian Haeussler ◽  
Tomasz J. Nowakowski ◽  
Arnold R. Kriegstein
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Radial Glia ◽  
Cortical Development ◽  
Cell Types ◽  
Human Cortex ◽  
Early Stages ◽  
Human Brain Development ◽  
Neuroepithelial Cells

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

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