Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis: [incl. Author Correction]

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis : [incl. Author Correction]. / 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.

In: Nature Communications, Vol. 11, No. 1, 5038, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

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: [incl. Author Correction]', Nature Communications, vol. 11, no. 1, 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: [incl. Author Correction]. Nature Communications, 11(1), [5038]. https://doi.org/10.1038/s41467-020-18752-7

Vancouver

Pfisterer U, Petukhov V, Demharter S, Meichsner J, Thompson JJ, Batiuk MY et al. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis: [incl. Author Correction]. Nature Communications. 2020;11(1). 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 : [incl. Author Correction]. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{8e40775bb6154131b7a3afd6a0baca66,
title = "Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis: [incl. Author Correction]",
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.",
keywords = "RNA-SEQ, MOUSE MODEL, PARVALBUMIN, NEOCORTEX, BRAIN, TRANSCRIPTOME, ABNORMALITIES, INTERNEURONS, EXCITABILITY, PERAMPANEL",
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",
note = "Author Correction: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis (Nature Communications, (2020), 11, 1, (5038) DOI: 10.1038/s41467-020-19869-5 https://www.nature.com/articles/s41467-020-19869-5",
year = "2020",
doi = "10.1038/s41467-020-18752-7",
language = "English",
volume = "11",
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

T2 - [incl. Author Correction]

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

N1 - Author Correction: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis (Nature Communications, (2020), 11, 1, (5038) DOI: 10.1038/s41467-020-19869-5 https://www.nature.com/articles/s41467-020-19869-5

PY - 2020

Y1 - 2020

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.

KW - RNA-SEQ

KW - MOUSE MODEL

KW - PARVALBUMIN

KW - NEOCORTEX

KW - BRAIN

KW - TRANSCRIPTOME

KW - ABNORMALITIES

KW - INTERNEURONS

KW - EXCITABILITY

KW - PERAMPANEL

UR - https://doi.org/10.1038/s41467-020-19869-5

U2 - 10.1038/s41467-020-18752-7

DO - 10.1038/s41467-020-18752-7

M3 - Journal article

C2 - 33028830

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5038

ER -

ID: 250484242