Evidence map›Paper›PMID 36274170›Full record

ArticleActa neuropathologica communications2022

High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy.

Balagopal Pai, Jessica Tome-Garcia, Wan Sze Cheng, German Nudelman, Kristin G Beaumont, Saadi Ghatan, Fedor Panov, Elodia Caballero, Kwadwo Sarpong, Lara Marcuse and 8 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 36 citations in OpenAlex.

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  5. Reprogramming of neuronal genome function and phenotype by astrocytes.bioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

Balagopal PaiDepartment of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Jessica Tome-GarciaDepartment of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Wan Sze ChengDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
German NudelmanDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Kristin G BeaumontDepartment of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Saadi GhatanDepartment of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Fedor PanovDepartment of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Elodia CaballeroDepartment of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Kwadwo SarpongDepartment of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Lara MarcuseDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Jiyeoun YooDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Yan JiangDepartment of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Anne SchaeferDepartment of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Schahram AkbarianDepartment of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Robert SebraDepartment of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Dalila PintoDepartment of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Elena ZaslavskyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. elena.zaslavsky@mssm.edu.
Nadejda M TsankovaDepartment of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. nadejda.tsankova@mssm.edu.
Icahn School of Medicine at Mount Sinai · USAllen Institute for Brain Science · USCenter for Genomic Science · IT

Funding

Integrative genomics to map risk genes and pathways in autism and epilepsyR01MH110555 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PINTO, DALILA · 2016 to 2020
$3.9M
Resolving SARS-Cov-2 tropism and COVID19 pathology in the brainR01NS106229 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Nadejda Mincheva Tsankova · 2019 to 2026
$3.5M
COVID and Translational Science supercomputer (CATS)S10OD030463 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2021 to 2021
$2.0M
Chromatin Plasticity, Transcriptional Activity and Kinetics in Developing and Adult Human Astrocyte and Oligodendroglial LineagesRF1DA048810 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TSANKOVA, NADEJDA MINCHEVA · 2019 to 2019
$1.8M
Profiling Glial and Neuronal Changes in Chromatin Accessibility and Transcriptional Dynamics in Drug-Resistant Human EpilepsyR03NS101581 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TSANKOVA, NADEJDA MINCHEVA · 2017 to 2018
$170k
NIDA NIH HHS RF1 DA048810NIH HHS S10 OD030463NIMH NIH HHS R01 MH110555NINDS NIH HHS R01 NS106229NINDS NIH HHS R03 NS101581
6 · The paper itself

Abstract

The pathophysiology of epilepsy underlies a complex network dysfunction between neurons and glia, the molecular cell type-specific contributions of which remain poorly defined in the human disease. In this study, we validated a method that simultaneously isolates neuronal (NEUN +), astrocyte (PAX6 + NEUN-), and oligodendroglial progenitor (OPC) (OLIG2 + NEUN-) enriched nuclei populations from non-diseased, fresh-frozen human neocortex and then applied it to characterize the distinct transcriptomes of such populations isolated from electrode-mapped temporal lobe epilepsy (TLE) surgical samples. Nuclear RNA-seq confirmed cell type specificity and informed both common and distinct pathways associated with TLE in astrocytes, OPCs, and neurons. Compared to postmortem control, the transcriptome of epilepsy astrocytes showed downregulation of mature astrocyte functions and upregulation of development-related genes. To gain further insight into glial heterogeneity in TLE, we performed single cell transcriptomics (scRNA-seq) on four additional human TLE samples. Analysis of the integrated TLE dataset uncovered a prominent subpopulation of glia that express a hybrid signature of both reactive astrocyte and OPC markers, including many cells with a mixed GFAP + OLIG2 + phenotype. A further integrated analysis of this TLE scRNA-seq dataset and a previously published normal human temporal lobe scRNA-seq dataset confirmed the unique presence of hybrid glia only in TLE. Pseudotime analysis revealed cell transition trajectories stemming from this hybrid population towards both OPCs and reactive astrocytes. Immunofluorescence studies in human TLE samples confirmed the rare presence of GFAP + OLIG2 + glia, including some cells with proliferative activity, and functional analysis of cells isolated directly from these samples disclosed abnormal neurosphere formation in vitro. Overall, cell type-specific isolation of glia from surgical epilepsy samples combined with transcriptomic analyses uncovered abnormal glial subpopulations with de-differentiated phenotype, motivating further studies into the dysfunctional role of reactive glia in temporal lobe epilepsy.

Indexed as

Epilepsy, Temporal LobeAstrocytesHumansNeurogliaRNA, NuclearTranscriptomeRNA, Nuclear

Identifiers

PMID36274170
PMCPMC9590125
OpenAlexW4307279203

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.