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SRX16459251: GSM6376808: Control 501, frontal lobe, bulk RNAseq; Homo sapiens; RNA-Seq
1 ILLUMINA (NextSeq 500) run: 50.5M spots, 14.6G bases, 4.4Gb downloads

External Id: GSM6376808_r1
Submitted by: Molecular Neurogenetics, Wallenberg Neuroscience Center, Lund University
Study: Single-cell transcriptomics of resected human traumatic brain injury tissues reveals acute activation of endogenous retroviruses in oligodendroglia
show Abstracthide Abstract
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
Sample: Control 501, frontal lobe, bulk RNAseq
SAMN29900436 • SRS14095313 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM6376808
Instrument: NextSeq 500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Surgically removed brain tissue was immediately placed in a sterile pre-labelled container and subsequently stored in -80_C freezer until analyzed. Half of the tissue was put in a routinely used fixative, 4% buffered formalin (Histo- Lab Products AB, Gothenburg, Sweden, catalogue no 02176). The samples were fixed for 24–72 h and then paraffin-embedded and processed by hardware Tissue tek VIP (Sakura, CA, USA). From the fresh frozen contused brain tissue, samples of ca 5mm2 were taken for scRNA sequencing. Single nuclei RNAseq: Protocol based on published nuclei isolation protocol (Södersten et al., 2018). Around 20 μg of -80 C-conserved tissue were thawed and dissociated in ice-cold lysis buffer (0.32M sucrose, 5 mM CaCl2, 3 mM MgAc, 0.1 mM Na2EDTA, 10 mM Tris-HCl pH 8.0, 1 mM DTT) using a 1 ml glass douncer (Wheaton). The homogenate was slowly and carefully layered in the centrifuge tubes on top of a sucrose layer (1.8 M sucrose, 3 mM MgAc, 10 mM Tris-HCl pH 8.0, 1 mM DTT) to create a gradient, and then centrifuged at 15500 rpm for 2 h 15 min. Following centrifugation, the supernatant was removed and the pellet softened for 10 minutes in 100 μl of nuclear storage buffer (15% sucrose, 10 mM Tris-HCl pH 7.2, 70 mM KCl, 2 mM MgCl2) prior resuspension in 300 μl of dilution buffer (10 mM Tris-HCl pH 7.2, 70 mM KCl, 2 mM MgCl2, Draq7 1:1000). The suspension was then filtered (70 μm cell strainer) and sorted via FACS (FACS Aria III, BD Biosciences) at 4° C with low flowrate, using a 100 μm nozzle (Pipette tips and Eppendorf tubes for transferring nuclei were pre-coated with 1% BSA). Bulk RNAseq: Total RNA was isolated from nuclei using the RNeasy Mini Kit (Qiagen). Single nuclei RNAseq: 8500 nuclei were sorted for single-nuclei RNA-sequencing and then loaded onto the Chromium Next GEM Single Cell 3' Kit (10x Genomics). Sequencing libraries samples were multiplexed and sequenced on a Novaseq machine using a 150-cycle kit using the recommended read length from 10x Genomics. Bulk RNAseq: Libraries were generated using Illumina TruSeq Stranded mRNA library prep kit (poly-A selection) and were sequenced on an Illumina NextSeq500 machine (paired-end 2×150bp).
Runs: 1 run, 50.5M spots, 14.6G bases, 4.4Gb
Run# of Spots# of BasesSizePublished
SRR2042665550,527,11914.6G4.4Gb2023-03-03

ID:
23183832

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