Abstract
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.
Highlights
Lead is largely used in industry and is very toxic to biological systems
Data from 26 RNA-seq of human embryonic-derived neural progenitor cells (ES-NP cells) samples treated with lead acetate 30 μM in a time-series experiment and 27 respective control samples were obtained from Gene Expression Omnibus (Jiang et al, 2017)
ES-NP cells are neural progenitor cells able to differentiate into neurons and glial cells (Selvaraj et al, 2012) and the modified protocol used by Jiang and collaborators points to neuronal differentiation (Chambers et al, 2009; Jiang et al, 2017)
Summary
Lead is largely used in industry and is very toxic to biological systems. This heavy metal accumulates in hard tissues, remaining in bones and teeth for decades (Ronis et al, 2001). Lead systemic effects can be observed through a wide range of lead poisoning symptoms. It includes anemia, abdominal pain, vomiting, cardiovascular system impairment, nephropathies, and abnormal spermatogenesis (Flora et al, 2012; Mitra et al, 2017). Several studies describe lead toxicity in central nervous system as well as its relation to irreversible brain development impairment (Finkelstein et al, 1998; Baranowska-Bosiacka et al, 2012; Stansfield et al, 2012).
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