A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice
Abstract
:1. Introduction
2. Results
2.1. Analysis of Transcriptional Profile of the Spinal Cord from Early Symptomatic Disease Stage SOD1G93A Mice
2.2. “Lipid Metabolism” Is a Biological Process That Is Transcriptionally Dysregulated in the Spinal Cord of SOD1G93A Mice at P90
2.3. Meta-Analysis of RNA-seq Datasets from Spinal Cord of SOD1 Mice at Early and Late Symptomatic Disease Stages
2.4. Meta-Analysis of RNA-seq Datasets Evidences Alterations in Lipid Metabolic Processes in the Spinal Cord of SOD1 Mice
2.5. Metabolic Pathways of Cholesterol, Phospholipids, Ceramides, and Icosanoids Are Transcriptionally Altered at Early Symptomatic Disease Stage in the Spinal Cord of SOD1 Mice
2.6. The Transcriptional Dysregulation of Lipid Pathways in the Spinal Cord of SOD1 Mice Is Exacerbated at Late Disease Stage
2.7. The Ch25h Gene Is an Early Marker of Lipid Alteratios in the Spinal Cord of SOD1 Mice
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. RNA Extraction and Sequencing
4.3. RNA-seq Data Processing
4.4. Functional Enrichment Analysis
4.5. RNA-seq Databases Selected for the Meta-Analysis
4.6. Meta-Analysis of Combined RNA-seq Studies
4.7. Protein–Protein Interaction Network
4.8. Pathway Analysis
4.9. Quantitative PCR
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Upregulated Genes | ||
GO Term | Biological Process | FDR-Value 1 |
GO:0002237 | response to molecule of bacterial origin | <1 × 10−13 |
GO:0071216 | cellular response to biotic stimulus | <1 × 10−13 |
GO:0002274 | myeloid leukocyte activation | <1 × 10−13 |
GO:0002443 | leukocyte mediated immunity | 1.80 × 10−13 |
GO:0001819 | positive regulation of cytokine production | 1.06 × 10−12 |
GO:0006909 | phagocytosis | 1.37 × 10−12 |
GO:0070661 | leukocyte proliferation | 5.78 × 10−12 |
GO:0002250 | adaptive immune response | 2.01 × 10−11 |
Downregulated Genes | ||
GO Term | Biological Process | FDR-Value 1 |
GO:0099177 | regulation of trans-synaptic signaling | 2.58 × 10−6 |
GO:0042391 | regulation of membrane potential | 4.27 × 10−5 |
GO:0051656 | establishment of organelle localization | 1.29 × 10−4 |
GO:0061564 | axon development | 1.29 × 10−4 |
GO:0051648 | vesicle localization | 1.57 × 10−4 |
GO:0099504 | synaptic vesicle cycle | 1.64 × 10−4 |
GO:0006836 | neurotransmitter transport | 3.4 × 10−4 |
GO:0006887 | exocytosis | 3.99 × 10−4 |
GO Term | Biological Process | FDR-Value 1 |
---|---|---|
GO:0071402 | cellular response to lipoprotein particle stimulus | 2.86 × 10−6 |
GO:0055094 | response to lipoprotein particle | 1.11 × 10−5 |
GO:0036314 | response to sterol | 5.13 × 10−4 |
GO:0019216 | regulation of lipid metabolic process | 0.009 |
GO:0006638 | neutral lipid metabolic process | 0.037 |
GO:0046486 | glycerolipid metabolic process | 0.039 |
Study | Dataset | Platform | Tissue | Age | Sample Size |
---|---|---|---|---|---|
Study 1 | Our study | Ilumina NovaSeq 6000 | Mouse spinal cord (lumbar) | 90 days | 5 WT 5 SOD1G93A (females) |
Study 2 | GSE43879 | Ilumina Genome Analyzer II | Mouse spinal cord (unspecified region) | 95 days | 2 WT 2 SOD1G93A (both sexes) |
Study 3 | GSE106364 | Ilumina HiSeq 4000 | Mouse spinal cord (lumbar) | 90 days | 5 WT 5 SOD1G86R (females) |
Study 4 | GSE106803 | Ilumina HiSeq 2000 | Mouse spinal cord (unspecified region) | 5 months | 3 WT 3 SOD1G93A (both sexes) |
Study 5 | GSE100888 | Ilumina HiSeq 2000 | Mouse spinal cord (lumbar) | 5 months | 4 WT 4 SOD1G93A (both sexes) |
Study 6 | GSE433879 | Ilumina Genome Analyzer II | Mouse spinal cord (unspecified region) | 4 months | 2 WT 2 SOD1G93A (both sexes) |
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Fernández-Beltrán, L.C.; Godoy-Corchuelo, J.M.; Losa-Fontangordo, M.; Williams, D.; Matias-Guiu, J.; Corrochano, S. A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice. Int. J. Mol. Sci. 2021, 22, 9553. https://doi.org/10.3390/ijms22179553
Fernández-Beltrán LC, Godoy-Corchuelo JM, Losa-Fontangordo M, Williams D, Matias-Guiu J, Corrochano S. A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice. International Journal of Molecular Sciences. 2021; 22(17):9553. https://doi.org/10.3390/ijms22179553
Chicago/Turabian StyleFernández-Beltrán, Luis C., Juan Miguel Godoy-Corchuelo, Maria Losa-Fontangordo, Debbie Williams, Jorge Matias-Guiu, and Silvia Corrochano. 2021. "A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice" International Journal of Molecular Sciences 22, no. 17: 9553. https://doi.org/10.3390/ijms22179553