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Updated: Jan 7, 2026
Facilitating Cerebral Organoid Culture via Lateral Soft Light Illumination
Published on: June 6, 2022
Soman-induced neurotoxicity in human iPSC-derived cerebral organoids: A whole-transcriptome analysis of ceRNA
Yue Wei1, Jingjing Shi2, Xuejun Chen2
1State Key Laboratory of Chemistry for NBC Hazards Protection, Beijing 102205, PR China; College of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, PR China.
Abstract:
Traditional animal models present challenges in fully elucidating chemical-induced neurotoxicity and its underlying mechanisms in humans due to physiological and genetic differences between species. To transcend inherent species limitations, cerebral organoids were differentiated from human induced pluripotent stem cells as a human-relevant model to delineate the neurotoxic profile of soman, classified among the most potent organophosphorus nerve agents. Organoid cell diversity and architecture were assessed via immunofluorescence and single-cell RNA sequencing. A 24-hour soman exposure elicited significant nerve damage in cerebral organoids, characterized by TUNEL assay-confirmed apoptosis and Fluoro-Jade C-stained neuronal degeneration. Whole transcriptome sequencing revealed 1012 differentially expressed mRNAs, 78 differentially expressed miRNAs and 203 differentially expressed long non-coding RNAs between the soman-exposed and control groups. Bioinformatics research suggested that the differentially expressed mRNAs were linked to axon guidance, long-term potentiation, and calcium signaling pathways. Furthermore, we constructed a competive endogenous RNA network including lncRNAs, miRNAs, and mRNAs, identifying two hub lncRNAs, two hub miRNAs, and 16 key mRNAs. This regulatory network implicates soman neurotoxicity in neuroinflammation and synaptic plasticity alterations, while validating glutamate receptor dysregulation and calcium homeostasis disruption as critical pathological mediators. Concurrently, it identifies the associated lncRNAs and miRNAs as potential biomarkers and therapeutic targets for soman-induced neuronal injury. Our findings elucidate the neurotoxic effects of soman in cerebral organoids at tissue, cellular, gene expression, and regulatory network levels. This work advances our knowledge of the underlying biological processes of soman exposure by offering new insights into prospective biomarkers and treatment targets.
Insights
Human cerebral organoids reveal soman's neurotoxicity, causing nerve damage and altering gene expression. This research identifies potential biomarkers and therapeutic targets for organophosphorus nerve agent injury.
Area of Science:
- Neuroscience
- Toxicology
- Biotechnology
Background:
- Traditional animal models inadequately represent human neurotoxicity due to species differences.
- Organophosphorus nerve agents, like soman, pose significant health risks requiring better human-relevant models.
Purpose of the Study:
- To investigate the neurotoxic effects of soman using human cerebral organoids.
- To identify molecular mechanisms and potential biomarkers of soman-induced neurotoxicity.
Main Methods:
- Human induced pluripotent stem cells were differentiated into cerebral organoids.
- Organoids were exposed to soman and analyzed using immunofluorescence, single-cell RNA sequencing, and transcriptome sequencing.
- Bioinformatics and competitive endogenous RNA network analysis were performed.
Main Results:
- Soman exposure induced apoptosis and neuronal degeneration in cerebral organoids.
- Significant changes in mRNA, miRNA, and lncRNA expression were observed.
- A regulatory network implicated neuroinflammation, synaptic plasticity, glutamate receptor dysregulation, and calcium homeostasis disruption.
Conclusions:
- Human cerebral organoids provide a relevant model for studying soman neurotoxicity.
- Identified molecular pathways and regulatory networks offer insights into soman's pathological mechanisms.
- Specific lncRNAs and miRNAs show promise as biomarkers and therapeutic targets for soman neurotoxicity.
