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Tytuł pozycji:

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

Tytuł:
Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis.
Autorzy:
Pfisterer U; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Petukhov V; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Demharter S; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Meichsner J; Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Thompson JJ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Batiuk MY; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Asenjo-Martinez A; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Vasistha NA; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Thakur A; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Mikkelsen J; Department of Neurology and Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Adorjan I; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
Pinborg LH; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, 2200, Copenhagen, Denmark.; Epilepsy Clinic, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, 2200, Copenhagen, Denmark.
Pers TH; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
von Engelhardt J; Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Kharchenko PV; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Khodosevich K; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. .
Źródło:
Nature communications [Nat Commun] 2020 Oct 07; Vol. 11 (1), pp. 5038. Date of Electronic Publication: 2020 Oct 07.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [London] : Nature Pub. Group
MeSH Terms:
Drug Resistant Epilepsy/*genetics
Epilepsy, Temporal Lobe/*genetics
Neurons/*pathology
Temporal Lobe/*pathology
Transcriptome/*genetics
Adolescent ; Adult ; Biopsy ; Case-Control Studies ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Datasets as Topic ; Drug Resistant Epilepsy/diagnosis ; Drug Resistant Epilepsy/pathology ; Drug Resistant Epilepsy/surgery ; Epilepsy, Temporal Lobe/diagnosis ; Epilepsy, Temporal Lobe/pathology ; Epilepsy, Temporal Lobe/surgery ; Female ; Glutamic Acid/metabolism ; Humans ; Magnetic Resonance Imaging ; Male ; Microdissection ; Middle Aged ; Models, Genetic ; Nerve Net/metabolism ; Nerve Net/pathology ; Neurons/cytology ; Neurons/metabolism ; RNA-Seq ; Receptors, AMPA/genetics ; Receptors, AMPA/metabolism ; Receptors, Glutamate/genetics ; Receptors, Glutamate/metabolism ; Signal Transduction/genetics ; Single-Cell Analysis ; Temporal Lobe/cytology ; Temporal Lobe/diagnostic imaging ; Temporal Lobe/surgery ; Transcription, Genetic ; Up-Regulation ; Young Adult
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Substance Nomenclature:
0 (Receptors, AMPA)
0 (Receptors, Glutamate)
3KX376GY7L (Glutamic Acid)
Entry Date(s):
Date Created: 20201008 Date Completed: 20201027 Latest Revision: 20211007
Update Code:
20240105
PubMed Central ID:
PMC7541486
DOI:
10.1038/s41467-020-18752-7
PMID:
33028830
Czasopismo naukowe
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.
Erratum in: Nat Commun. 2020 Nov 19;11(1):5988. (PMID: 33214565)
Comment in: Epilepsy Curr. 2021 Mar;21(2):124-125. (PMID: 33508978)

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