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Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
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Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
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Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
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Journal Article
Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
2020
Overview
Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.
The pathophysiology of epilepsy is unclear. Here, the authors present single-nuclei transcriptomic profiling of human temporal lobe epilepsy from patients. They identified epilepsy-associated neuronal subtypes, and a panel of dysregulated genes, predicting neuronal circuits contributing to epilepsy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/91
/ Adult
/ Biopsy
/ Circuits
/ Drug Resistant Epilepsy - diagnosis
/ Drug Resistant Epilepsy - genetics
/ Drug Resistant Epilepsy - pathology
/ Drug Resistant Epilepsy - surgery
/ Epilepsy
/ Epilepsy, Temporal Lobe - diagnosis
/ Epilepsy, Temporal Lobe - genetics
/ Epilepsy, Temporal Lobe - pathology
/ Epilepsy, Temporal Lobe - surgery
/ Female
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Receptors, AMPA - metabolism
/ Receptors, Glutamate - genetics
/ Receptors, Glutamate - metabolism
/ RNA-Seq
/ Science
/ Seizures
/ Signal Transduction - genetics
/ Temporal Lobe - diagnostic imaging
/ α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
/ α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
