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

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.

Transcriptogram analysis reveals relationship between viral titer and gene sets responses during Corona-virus infection

“…Our Transcriptogram method to quantify whole-genome-level expression changes reduces noise and enhances signal-to-noise ratio in transcriptome analyses, increasing the power of statistical tests to identify significantly affected pathways and timescales ( 6 ). Transcriptograms provide a high-level visualization of significant changes in gene expression and have been proved useful in identifying relationships between pathways in fungi ( 7 , 8 ), plants ( 9 , 10 ), and humans ( 11 , 12 , 6 ), eventually coming up with association between gene sets or biological functions that are new in the literature ( 11 ). The Transcriptogramer software tool is freely available for download at https://lief.if.ufrgs.br/pub/biosoftwares/transcriptogramer/ and has a Bioconductor application ( 13 ).…”

Transcriptogram analysis reveals relationship between viral titer and gene sets responses during Corona-virus infection

“…Transcriptograms provide a high-level visualization of significant changes in gene expression and have proved useful in identifying relationships between pathways in fungi [8,9], plants [10,11], and humans [12,13,7]. The Transcriptogramer software tool is freely available for download at https://lief.if.ufrgs.br/pub/biosoftwarestranscriptogramer/ and has a Bioconductor application [14].…”

“…Our Transcriptogram method to quantify whole-genome-level expression changes reduces noise and enhances signal-to-noise ratio in transcriptome analyses, increasing the power of statistical tests to identify significantly affected pathways and timescales [6]. Transcriptograms provide a high-level visualization of significant changes in gene expression and have proved useful in identifying relationships between pathways in fungi [7,8], plants 9,10, and humans [11,12,6]. The Transcriptogramer software tool is freely available for download at https://lief.if.ufrgs.br/pub/biosoftwares/transcriptogramer/ and has a Bioconductor application [13].…”