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Title:
Single cell molecular alterations reveal target cells and pathways of concussive brain injury | Nature Communications
Description:
The complex neuropathology of traumatic brain injury (TBI) is difficult to dissect, given the convoluted cytoarchitecture of affected brain regions such as the hippocampus. Hippocampal dysfunction during TBI results in cognitive decline that may escalate to other neurological disorders, the molecular basis of which is hidden in the genomic programs of individual cells. Using the unbiased single cell sequencing method Drop-seq, we report that concussive TBI affects previously undefined cell populations, in addition to classical hippocampal cell types. TBI also impacts cell type-specific genes and pathways and alters gene co-expression across cell types, suggesting hidden pathogenic mechanisms and therapeutic target pathways. Modulating the thyroid hormone pathway as informed by the T4 transporter transthyretin Ttr mitigates TBI-associated genomic and behavioral abnormalities. Thus, single cell genomics provides unique information about how TBI impacts diverse hippocampal cell types, adding new insights into the pathogenic pathways amenable to therapeutics in TBI and related disorders. Traumatic brain injury (TBI) affects the hippocampus and can lead to neurological and psychiatric disorders. Here, the authors perform single-cell RNA sequencing to reveal molecular pathways across a range of cell types affected during TBI.
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cell, cells, genes, gene, types, mtbi, tbi, article, brain, fig, google, scholar, expression, type, degs, injury, single, sham, hippocampal, marker, markers, pathways, cas, data, neurons, specific, target, supplementary, dropseq, neuronal, traumatic, ttr, treatment, test, analysis, usa, samples, nature, clusters, images, potential, ependymal, information, molecular, hippocampus, coexpression, patterns, deg, pyramidal, number,
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nature portfolio n-methyl-d-aspartate receptor signaling privacy policy /wp-content/uploads/2016/03/drop-seqalignmentcookbookv1 animal research committee basic helix-loop-helix mrnas advertising sparse nature unique tgf-Ξ²-dependent molecular traditional t-sne-based approaches14 social media drop-seq data pre-processing nature 407 nature 445 nature author information authors solutions reprints fernando gomez-pinilla 8βbp index read visualizing high-dimensional data sodium-dependent phosphate transporter drop-seq sequencing data illumina high-throughput sequencing beta-catenin-n-cadherin saturated-fat diet aggravates temper post-traumatic epilepsy refractive indexβ1 original author density-based spatial clustering drop-seq libraries subtype-specific expression patterns adult ventricular-subventricular zone post-traumatic stress disorder major brain-specific substrate open gender-dependent transthyretin modulation facilitate future development nuclearly-encoded humanin isoforms single-cell rna-seq blood-brain barrier breakdown bulk tissue rna-sequencing 11 days post-injury/treatment drop-seq defined markers brain amyloid-beta levels cell-type specific manner cell-type specific genes traumatic brain injuries library fragment length cell type-specific degs
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- Dementia resulting from traumatic brain injury: what is the pathology?
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headline:Single cell molecular alterations reveal target cells and pathways of concussive brain injury
description:The complex neuropathology of traumatic brain injury (TBI) is difficult to dissect, given the convoluted cytoarchitecture of affected brain regions such as the hippocampus. Hippocampal dysfunction during TBI results in cognitive decline that may escalate to other neurological disorders, the molecular basis of which is hidden in the genomic programs of individual cells. Using the unbiased single cell sequencing method Drop-seq, we report that concussive TBI affects previously undefined cell populations, in addition to classical hippocampal cell types. TBI also impacts cell type-specific genes and pathways and alters gene co-expression across cell types, suggesting hidden pathogenic mechanisms and therapeutic target pathways. Modulating the thyroid hormone pathway as informed by the T4 transporter transthyretin Ttr mitigates TBI-associated genomic and behavioral abnormalities. Thus, single cell genomics provides unique information about how TBI impacts diverse hippocampal cell types, adding new insights into the pathogenic pathways amenable to therapeutics in TBI and related disorders. Traumatic brain injury (TBI) affects the hippocampus and can lead to neurological and psychiatric disorders. Here, the authors perform single-cell RNA sequencing to reveal molecular pathways across a range of cell types affected during TBI.
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