{"doi":"10.1101/2020.12.11.421370","title":"Cell type-specific isolation and transcriptomic profiling informs glial pathology in human temporal lobe epilepsy","abstract":"SUMMARY The pathophysiology of epilepsy underlies complex network dysfunction, the cell-type-specific contributions of which remain poorly defined in human disease. In this study, we developed a strategy that simultaneously isolates neuronal, astrocyte and oligodendroglial progenitor (OPC)-enriched nuclei from human fresh-frozen neocortex and applied it to characterize the distinct transcriptome of each cell type in temporal lobe epilepsy (TLE) surgical samples. Differential RNA-seq analysis revealed several dysregulated pathways in neurons, OPCs, and astrocytes, and disclosed an immature phenotype switch in TLE astrocytes. An independent single cell RNA-seq TLE dataset uncovered a hybrid population of cells aberrantly co-expressing canonical astrocyte and OPC-like progenitor markers (GFAP+OLIG2+ glia), which we corroborated in-situ in human TLE samples, and further demonstrated their emergence after chronic seizure injury in a mouse model of status epilepticus. In line with their immature signature, a subset of human TLE glia were also abnormally proliferative, both in-vivo and in-vitro. Generally, this analysis validates the utility of the proposed cell type-specific isolation strategy to study glia-specific changes ex vivo using fresh-frozen human samples, and specifically, it delineates an aberrant glial phenotype in human TLE specimens.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123183,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9422,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":272089,"name":"German Nudelman","orcid":"0000-0002-5344-5981","position":1,"is_corresponding":false},{"id":566550,"name":"Zarmeen Mussa","orcid":null,"position":2,"is_corresponding":false},{"id":566551,"name":"Elodia Caballero","orcid":null,"position":3,"is_corresponding":false},{"id":424239,"name":"Yan Jiang","orcid":"0000-0002-1507-8690","position":4,"is_corresponding":false},{"id":89997,"name":"Kristin G. Beaumont","orcid":"0000-0003-3075-9977","position":5,"is_corresponding":false},{"id":228095,"name":"Ying‐Chih Wang","orcid":"0000-0003-3984-502X","position":6,"is_corresponding":false},{"id":2004,"name":"Robert Sebra","orcid":"0000-0001-9267-2426","position":7,"is_corresponding":false},{"id":21362,"name":"Schahram Akbarian","orcid":"0000-0001-7700-0891","position":8,"is_corresponding":false},{"id":308808,"name":"Dalila Pinto","orcid":"0000-0002-8769-0846","position":9,"is_corresponding":false},{"id":34968,"name":"Elena Zaslavsky","orcid":"0000-0002-4828-7771","position":10,"is_corresponding":false},{"id":2003,"name":"Nadejda M. Tsankova","orcid":"0000-0002-5333-312X","position":11,"is_corresponding":false},{"id":565873,"name":"Jessica Tomé-García","orcid":"0000-0003-0554-8676","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:14:59.547352Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}