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Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis

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Harvard

Pfisterer, U, Petukhov, V, Demharter, S, Meichsner, J, Thompson, JJ, Batiuk, MY, Martinez, AA, Vasistha, NA, Thakur, A, Mikkelsen, J, Adorjan, I, Pinborg, LH, Pers, TH, von Engelhardt, J, Kharchenko, PV & Khodosevich, K 2020, 'Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis', Nature Communications, bind 11, nr. 1, 5038, s. 5038. https://doi.org/10.1038/s41467-020-18752-7

APA

Pfisterer, U., Petukhov, V., Demharter, S., Meichsner, J., Thompson, J. J., Batiuk, M. Y., Martinez, A. A., Vasistha, N. A., Thakur, A., Mikkelsen, J., Adorjan, I., Pinborg, L. H., Pers, T. H., von Engelhardt, J., Kharchenko, P. V., & Khodosevich, K. (2020). Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. Nature Communications, 11(1), 5038. [5038]. https://doi.org/10.1038/s41467-020-18752-7

CBE

Pfisterer U, Petukhov V, Demharter S, Meichsner J, Thompson JJ, Batiuk MY, Martinez AA, Vasistha NA, Thakur A, Mikkelsen J, Adorjan I, Pinborg LH, Pers TH, von Engelhardt J, Kharchenko PV, Khodosevich K. 2020. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. Nature Communications. 11(1):5038. https://doi.org/10.1038/s41467-020-18752-7

MLA

Vancouver

Pfisterer U, Petukhov V, Demharter S, Meichsner J, Thompson JJ, Batiuk MY o.a. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. Nature Communications. 2020 okt 7;11(1):5038. 5038. https://doi.org/10.1038/s41467-020-18752-7

Author

Pfisterer, Ulrich ; Petukhov, Viktor ; Demharter, Samuel ; Meichsner, Johanna ; Thompson, Jonatan J ; Batiuk, Mykhailo Y ; Martinez, Andrea Asenjo ; Vasistha, Navneet A ; Thakur, Ashish ; Mikkelsen, Jens ; Adorjan, Istvan ; Pinborg, Lars H ; Pers, Tune H ; von Engelhardt, Jakob ; Kharchenko, Peter V ; Khodosevich, Konstantin. / Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. I: Nature Communications. 2020 ; Bind 11, Nr. 1. s. 5038.

Bibtex

@article{4ea41f86f20b48719982367dbcc6c6cd,
title = "Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis",
abstract = "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.",
author = "Ulrich Pfisterer and Viktor Petukhov and Samuel Demharter and Johanna Meichsner and Thompson, {Jonatan J} and Batiuk, {Mykhailo Y} and Martinez, {Andrea Asenjo} and Vasistha, {Navneet A} and Ashish Thakur and Jens Mikkelsen and Istvan Adorjan and Pinborg, {Lars H} and Pers, {Tune H} and {von Engelhardt}, Jakob and Kharchenko, {Peter V} and Konstantin Khodosevich",
year = "2020",
month = oct,
day = "7",
doi = "10.1038/s41467-020-18752-7",
language = "English",
volume = "11",
pages = "5038",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis

AU - Pfisterer, Ulrich

AU - Petukhov, Viktor

AU - Demharter, Samuel

AU - Meichsner, Johanna

AU - Thompson, Jonatan J

AU - Batiuk, Mykhailo Y

AU - Martinez, Andrea Asenjo

AU - Vasistha, Navneet A

AU - Thakur, Ashish

AU - Mikkelsen, Jens

AU - Adorjan, Istvan

AU - Pinborg, Lars H

AU - Pers, Tune H

AU - von Engelhardt, Jakob

AU - Kharchenko, Peter V

AU - Khodosevich, Konstantin

PY - 2020/10/7

Y1 - 2020/10/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85092317826&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-18752-7

DO - 10.1038/s41467-020-18752-7

M3 - Journal article

C2 - 33028830

VL - 11

SP - 5038

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5038

ER -

ID: 61072945