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Series GSE209552 Query DataSets for GSE209552
Status Public on Mar 03, 2023
Title Single-cell transcriptomics of resected human traumatic brain injury tissues reveals acute activation of endogenous retroviruses in oligodendroglia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used snRNA-seq to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides a unique insight into the initiating events of the neuroinflammatory response in TBI, which has new therapeutic implications.
 
Overall design To investigate changes in cell-type composition and cell-type specific transcriptional responses after severe, acute TBI in humans, we performed single-nucleus RNA sequencing (snRNA-seq) from fresh frozen human brain tissue. We recruited 12 severe TBI patients, defined as post resuscitation Glasgow Coma Scale (GCS) score ≤ 8. The mean age of TBI patients (10 males, 2 females) was 49.5 ± 18.2 years. In these patients decompressive surgery was a life-saving measure to remove injured and swollen space-occupying brain tissue causing marked mass effect or increased intracranial pressure (ICP) refractory to conservative, medical neurointensive care treatment. The injured and contused brain regions (typically the injured part of a temporal or frontal lobe) were surgically removed between 4 hours and 8 days after injury 20. The raw data of these patients is not included in the GEO repository as these are alive individuals protected by GDPR, processed files are available. As control tissue, we used five fresh-frozen post-mortem samples from the frontal and temporal lobe obtained from three non-neurological deaths aged 69, 75 and 87 years. We isolated nuclei from frozen human brain tissue using ultracentrifugation and FACS (see methods for details) and performed snRNA-seq using the 10X Genomics pipeline.

To investigate a mechanistic link between interferon activation and ERV expression we decided to perform in vitro experiments in human glial progenitor cells (hGPCs). We differentiated human embryonic stem cells (hESCs) into hGPCs using a 135-day differentiation protocol. The hGPCs were treated with interferon gamma (IFN?, 5ng/ml) for 48 hours before harvested for 2×150 bp paired-end, strand-specific bulk RNA-seq analysis.

***Raw data not provided for GSM6376811-GSM6376826 due to patient privacy concerns***

The records have been updated with the following files on Sep 5, 2023:
TBI_gene_count_matrix_2.csv
hGPC_gene_count_matrix_2.csv
 
Contributor(s) Garza R, Sharma Y, Atacho D, Thiruvalluvan A, Hamdeh SA, Jönsson M, Horvath V, Adami A, Ingelsson M, Jern P, Hammell MG, Englund E, Kirkeby A, Jakobsson J, Marklund N
Citation https://doi.org/10.1101/2022.09.07.506982
Submission date Jul 22, 2022
Last update date Sep 05, 2023
Contact name Johan Jakobsson
E-mail(s) johan.jakobsson@med.lu.se
Organization name Lund University
Department Wallenberg Neuroscience Center
Lab Molecular Neurogenetics
Street address Sölvegatan 17
City Lund
ZIP/Postal code 22362
Country Sweden
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (30)
GSM6376803 Control 501, frontal lobe, scRNAseq
GSM6376804 Control 501, temporal lobe, scRNAseq
GSM6376805 Control 529, frontal lobe, scRNAseq
Relations
BioProject PRJNA861257

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE209552_ERV_count_matrix_2.csv.gz 94.0 Kb (ftp)(http) CSV
GSE209552_RAW.tar 835.9 Mb (http)(custom) TAR (of BW, CSV, MTX, TSV)
GSE209552_TBI_HuBrainCTL_Nuclei501F_Hg38_TE_norm_cluster_size_matrix.csv.gz 51.9 Kb (ftp)(http) CSV
GSE209552_TBI_HuBrainCTL_Nuclei501T_Hg38_TE_norm_cluster_size_matrix.csv.gz 38.3 Kb (ftp)(http) CSV
GSE209552_TBI_HuBrainCTL_Nuclei502T_Hg38_TE_norm_cluster_size_matrix.csv.gz 56.3 Kb (ftp)(http) CSV
GSE209552_TBI_HuBrainCTL_Nuclei529F_Hg38_TE_norm_cluster_size_matrix.csv.gz 50.1 Kb (ftp)(http) CSV
GSE209552_TBI_HuBrainCTL_Nuclei529T_Hg38_TE_norm_cluster_size_matrix.csv.gz 50.9 Kb (ftp)(http) CSV
GSE209552_TBI_gene_count_matrix_2.csv.gz 5.5 Mb (ftp)(http) CSV
GSE209552_control_TE_norm_cluster_size_matrix.csv.gz 83.4 Kb (ftp)(http) CSV
GSE209552_control_TE_raw_matrix.csv.gz 35.9 Kb (ftp)(http) CSV
GSE209552_hGPC_gene_count_matrix_2.csv.gz 5.3 Mb (ftp)(http) CSV
GSE209552_tbi_TE_norm_cluster_size_matrix.csv.gz 76.2 Kb (ftp)(http) CSV
GSE209552_tbi_TE_raw_matrix.csv.gz 35.5 Kb (ftp)(http) CSV
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

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