Single Cell RNA Sequencing after Moderate Traumatic Brain Injury: Effects of Therapeutic Hypothermia
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ABSTRACT:
PROVIDER: PRJNA1226276 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32419425_1.fastq.gz | Fastqsanger.gz | |||
| SRR32419425_2.fastq.gz | Fastqsanger.gz | |||
| SRR32419426_1.fastq.gz | Fastqsanger.gz | |||
| SRR32419426_2.fastq.gz | Fastqsanger.gz | |||
| SRR32419427_1.fastq.gz | Fastqsanger.gz |
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Project description:Traumatic brain injury (TBI) initiates a cascade of cellular and molecular events that promote acute and long-term patterns of neuronal, glial, vascular, and synaptic vulnerability leading to lasting neurological deficits. These complex responses lead to patterns of programmed cell death, diffuse axonal injury, increased blood-brain barrier disruption, neuroinflammation, and reactive gliosis, each a potential target for therapeutic interventions. Posttraumatic therapeutic hypothermia (TH) has been reported to be highly protective after brain and spinal cord injury and studies have investigated molecular mechanisms underlying mild hypothermic protection while commonly assessing heterogenous cell populations. In this study we conducted single-cell RNA sequencing (scRNAseq) on cerebral cortical tissues after experimental TBI followed by a period of normothermia or hypothermia to clarify multiple cell type-specific transcriptional responses. C57BL/6 mice underwent moderate controlled cortical impact (CCI) injury or sham surgery and then placed under sustained normothermia (37⁰C) or hypothermia (33⁰C) for 2 hrs. After 24 hours, cortical tissues including peri-contused regions were processed for scRNAseq. Unbiased clustering and differential expression tests revealed cellular heterogeneity, reactive astrocytes, microglia, and leukocyte infiltration at this subacute posttraumatic time point. The analysis also revealed vascular and immune subtypes associated with neovascularization and debris clearance, respectively. Compared to normothermic conditions, TH treatment altered the abundance of specific cell subtypes and induced reactive astrocyte-specific modulation of neurotropic factor gene expression. In addition, an increase in the proportion of endothelial tip cells in the hypothermic TBI group was documented compared to normothermia. These data emphasize the importance of early temperature-sensitive glial and vascular cell processes in producing potentially neuroprotective downstream signaling cascades in a cell-type-dependent manner. The use of single cell sequencing to address cell-specific mechanisms underlying therapeutic treatments provides a valuable resource for identifying targetable biological pathways for the development of neuroprotective and reparative interventions.
2025-04-21 | GSE290150 | GEO
Project description:Background: Traumatic brain injury is a medical event of global concern, and a growing body of research suggests that circular RNA can play very important roles in traumatic brain injury. To explore the functions of more novel and valuable circular RNA in traumatic brain injury response, a moderate traumatic brain injury in rat was established and a comprehensive analysis of circular RNA expression profiles in rat cerebral cortex was done. Results: As a result, 301 up-regulated and 284 down-regulated circular RNAs were obtained in moderate traumatic brain injury rats, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed based on the circular RNA’s host genes, and a circRNA-miRNA interaction network based on differentially expressed circular RNAs was constructed. Also, four circular RNAs were validated by RT-qPCR and sanger sequencing. Conclusion: This study showed that differentially expressed circular RNAs existed between rat cerebral cortex after moderate traumatic brain injury and control. And this will provide valuable information for circular RNA research in the field of traumatic brain injury.
2022-01-15 | GSE193521 | GEO
Project description:Background: Moderate hypothermia (32oC for 12 – 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA. Methods: Acute monocytic leukemia THP-1 cells were incubated under control conditions (37oC) or moderate hypothermia (32oC) for 24 hours. Cellular mRNA was extracted and a cold stress response was confirmed by examining the expression of the cold-inducible gene CIRBP by reverse transcription PCR (RT-PCR). Gene expression analysis was performed on seven sets of samples with Affymetrix U133A chips, using established statistical methods. Sequences were considered to be affected by cold if they showed statistically significant changes in expression and also met published post-hoc filter criteria (changes in geometric mean expression of 2-fold or greater and detection calls of “present” or “marginal” in at least half of the experiments). The changes in expression of a select number of these sequences were further confirmed by PCR. Results: 167 sequences met our prospectively defined criteria for a change in expression; 67 showed increases in expression and 100 showed decreases in expression. Consistent with prior literature, the cold-inducible genes CIRBP and RBM3 showed increases in expression. Functional categories affected by cold stress included genes involved in immune responses, cell growth, proliferation, and differentiation, and metabolism and biosynthesis. Several heat shock proteins (HSPs) showed decreases in expression. Conclusions: Moderate hypothermia produces substantial changes in cellular gene expression, in categories potentially of importance to systemic function. Interestingly, cold exposure without re-warming decreased the expression of several HSPs. Our in vitro findings suggest that moderate hypothermia in vivo might produce physiologically important changes in gene expression by circulating leukocytes. Keywords: Stress response / hypothermia
2006-04-05 | GSE4425 | GEO
Project description:Time dependent-profiles in the gene expression level following lateral moderate fluid percussion injury in the rat brain We used microarray to elucidate relationship between the alteration of gene expression levels and the progression of brain damages following traumatic brain injury. To examine the levels of gene expression in the early phase of traumatic brain injury, we analyzed the gene expression at 3, 6, 12, and 48 h after trauma using the lateral moderate fluid percussion TBI model. The ratios of the gene expression level were compared between chips corresponding to the 3, 6 and 12 h fluid percussion groups and the sham group chips. On the other hand, the rations of gene expression level after 48 h FPI were compared with 48 h sham chip, because the gene expression levels of 48 h sham chip were distinct from sham group chips (3, 6 and 12 h) in the cluster and principal components analyses.
2010-12-07 | E-GEOD-24047 | biostudies-arrayexpress
Project description:Time dependent-profiles in the gene expression level following lateral moderate fluid percussion injury in the rat brain We used microarray to elucidate relationship between the alteration of gene expression levels and the progression of brain damages following traumatic brain injury.
2010-12-07 | GSE24047 | GEO
Project description:Comprehensive analysis of circRNA expression profiles in rat cerebral cortex after moderate traumatic brain injury
| PRJNA796539 | ENA
Project description:Background: Moderate hypothermia (32oC for 12 â 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA. Methods: Acute monocytic leukemia THP-1 cells were incubated under control conditions (37oC) or moderate hypothermia (32oC) for 24 hours. Cellular mRNA was extracted and a cold stress response was confirmed by examining the expression of the cold-inducible gene CIRBP by reverse transcription PCR (RT-PCR). Gene expression analysis was performed on seven sets of samples with Affymetrix U133A chips, using established statistical methods. Sequences were considered to be affected by cold if they showed statistically significant changes in expression and also met published post-hoc filter criteria (changes in geometric mean expression of 2-fold or greater and detection calls of âpresentâ or âmarginalâ in at least half of the experiments). The changes in expression of a select number of these sequences were further confirmed by PCR. Results: 167 sequences met our prospectively defined criteria for a change in expression; 67 showed increases in expression and 100 showed decreases in expression. Consistent with prior literature, the cold-inducible genes CIRBP and RBM3 showed increases in expression. Functional categories affected by cold stress included genes involved in immune responses, cell growth, proliferation, and differentiation, and metabolism and biosynthesis. Several heat shock proteins (HSPs) showed decreases in expression. Conclusions: Moderate hypothermia produces substantial changes in cellular gene expression, in categories potentially of importance to systemic function. Interestingly, cold exposure without re-warming decreased the expression of several HSPs. Our in vitro findings suggest that moderate hypothermia in vivo might produce physiologically important changes in gene expression by circulating leukocytes. Experiment Overall Design: Seven sets of paired THP-1 samples, grown under either control (37oC) or hypothermic (32oC) conditions for 24 hours
2007-10-26 | E-GEOD-4425 | biostudies-arrayexpress
Project description:Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32°C) or normothermia (37°C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia. Hypothermia was compared against normothermia at seven different time-points. Hypothermic and normothermic mouse embryonic fibroblasts (MEF, in 100 mm dishes, one array per time-point) were submitted to gene expression analysis using Mouse Gene 1.0 ST GeneChip® (Affymetrix) microarrays. Differential gene expression analysis was performed with R package DEMI (http://biit.cs.ut.ee/demi/).
2014-03-01 | E-GEOD-54229 | biostudies-arrayexpress
Project description:Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32°C) or normothermia (37°C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia.
2014-03-01 | GSE54229 | GEO
Project description:Transcriptomic changes in the pre-chiasmatic optic nerve, retrobulbar optic nerve of goats 1 day after hypothermia treatment of optic nerve crush injury
2022-02-24 | GSE197123 | GEO