DOI: 10.5281/zenodo.18603397
title: Arsenic Attenuates SIM-A9

description: Arsenic (As) is a major public health threat, with more than 200 million people at risk of consuming drinking water that exceeds World Health Organization safety guidelines. Given that inorganic arsenic (iAs) is linked to various neuropsychiatric and neurodegenerative disorders, a better understanding of its mechanisms of toxicity is warranted. Current evidence suggests that microglia are central to the pathophysiology of As-induced effects in the central nervous system. Microglia are resident immune cells in the brain that play a crucial role in surveillance, clearance of pathogens, and wound healing. They undergo distinct stages of development throughout life, and their behavior is known to be disrupted by environmental insults such as iAs. To characterize the mechanisms by which iAs alters microglial function, we examined the impact of subtoxic exposure to trivalent inorganic arsenic (As(III)) on microglial activity, both in the presence and absence of immune challenges, using a spontaneously immortalized murine cell line derived from the neonatal cerebral cortex (SIM-A9). Results indicate that iAs causes early activation of SIM-A9 cells through upregulation of toll-like receptor 4-mediated NF-kB signaling, followed by slower onset of anti-inflammatory effects mediated through increased Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) activity. This later attenuation of responses to inflammatory stimuli suggests that iAs exposure may impair microglial function and sensitize individuals to secondary challenges relevant to a range of neurological functions and disorders.
description: Four different conditions in SIM-A9 cells were sequenced following treatment as described in the publication.Samples are coded by letters and numbers. The key is listed below.

Vehicle (24 hours): A2, B3, C2, D1LPS (6 hours): A4, C4, C5, C6iAs (24 hours): C8, C9, CC7iAs+LPS (24 hours; 6 hours): B10, B12, C12, D11

Key.README.docx - provides Novogene's detailed descriptions of column headers for Differentially Expressed Gene (DEG) analysis files and Gene Ontology (GO) enrichment analysis files.gene_count_raw.xls - raw, unnormalized counts for each samplegene_fpkm_group.xls - counts normalized to Fragments per Kilobase of exon per Million mapped reads (FPKM) and then averaged per group. 

AsvsVehicle_deg.xls - List of genes that are differentially expressed in arsenic-treated cells relative to vehicle-treated cells.As_LPSvsLPS_deg.xls - List of genes that are differentially expressed in arsenic+LPS-treated cells relative to LPS-treated cells.

AsvsVehicle.all_GOenrich.xls - List of enriched GO terms when comparing arsenic-treated cells relative to vehicle-treated cells.

As_LPSvsLPS.all_GOenrich.xls - List of enriched GO terms when comparing arsenic+LPS-treated cells relative to LPS-treated cells.

AsvsVehicle.all_GOdot.png - GO plot of top enriched GO terms for arsenic-treated cells relative to vehicle-treated cells.

As_LPSvsLPS.all_GOdot.png - GO plot of top enriched GO terms for arsenic+LPS-treated cells relative to LPS-treated cells.

runDecoupler3_Dorothea.py - Annotated code used to generate Transcription Factory Enrichment Analysis data.

Database_dorothea.csv - Dorothea database of transcription factors and assigned scores for transcription factor enrichment analysis. 

As_vs_V_Decoupler_ULM_TF_Activity_Inference_Dorothea_MouseGenome.csv - Complete list of enriched transcription factors generated from Decoupler using RNA sequencing data from arsenic-treated cells relative to vehicle-treated cells.

AsLPS_vs_LPS_Decoupler_ULM_TF_Activity_Inference_Dorothea_MouseGenome.csv - Complete list of enriched transcription factors generated from Decoupler using RNA sequencing data from arsenic+LPS-treated cells relative to LPS-treated cells.As_vs_V_Decoupler_ULM_TF_Activity_Inference_Top52_NoSigFilt_Dorothea_MouseGenome.pdf - Transcription Factory Enrichment Activity plot depicting 52 most significant hits when comparing arsenic-treated cells to vehicle-treated cells. 

AsLPS_vs_LPS_Decoupler_ULM_TF_Activity_Inference_Top52_NoSigFilt_Dorothea_MouseGenome.pdf - Transcription Factory Enrichment Activity plot depicting 52 most significant hits when comparing arsenic+LPS-treated cells to LPS-treated cells.