Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells

Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate

Análise evolutiva do sistems antioxidante gênico de Arabidopsis thaliana

Reactive oxygen species (ROS) are byproducts of aerobic metabolism and may cause oxidative damage to biomolecules. Plants have a complex antioxidant system, involving enzymatic and non-enzymatic compounds, to protects against ROS exacerbated production. The evolutionary origin of enzymatic defense in plants is not totally clear. Here we describe an antioxidant gene network for A. thaliana and investigate the evolutionary origin of this network. We gathered from public repositories 208 A. thaliana genes directly involved with ROS detoxification and proposed an A. thaliana antioxidant gene network. Using orthology information of 238 Eukaryotes from STRINGdb we have inferred the evolutionary root of each gene to reconstruct the evolutionary history of A. thaliana antioxidant gene network. We found two interconnected clusters: one formed by SOD-related, Thiol-redox, and peroxidases; and other formed entirely by class III peroxidases. Each cluster emerged in different periods of evolution and class III peroxidases are the most recent components of the network. According to our results, class III peroxidases are in expansion throughout plant evolution.As espécies reativas de oxigênio (EROs) são conhecidos subprodutos do metabolismo aeróbio e apesar de ter função sinalizadora, sua produção exacerbada pode levar a dano celular. As plantas desenvolveram um sistema antioxidante complexo, formado por componentes enzimáticos e não-enzimáticos, para se proteger contra a superprodução de EROs. Porém, a evolução desse sistema antioxidante ainda não está clara. Aqui o objetivo do trabalho foi descrever uma rede gênica que modela o sistema antioxidante de Arabidopsis thaliana e também investigar sua origem evolutiva. Primeiramente foram obtidos os genes a partir de bancos de dados públicos como Gene Ontology, que tivessem uma relação direta com a remoção de EROs dos sistemas, bem como alguns substratos/produtos. Então, foi modelada uma rede de interação proteína-proteína para A. thaliana. Posteriormente, utilizando informação de ortologia de 238 espécies anotadas no STRING, pudemos inferir a raiz evolutiva de cada um dos genes a fim de reconstruir a história evolutiva da rede gênica antioxidante de A. thaliana. Na rede construída, dois grupos interconectados foram encontrados, sendo um formado por proteínas SOD, tiol-redox e peroxidases; outro formado unicamente por peroxidases classe III. Cada um dos grupos provavelmente teve sua origem em momentos diferentes da escala evolutiva, porém as peroxidases classe III se mostraram os componentes mais recentes da rede. De acordo com nossos resultados, esse grupo de genes continua em expansão ao longo da evolução das plantas

Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells

Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate