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| Status |
Public on May 24, 2021 |
| Title |
Altered oligodendroglia and astroglia in chronic traumatic encephalopathy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head injury. Brain white matter atrophy and axonal loss have been reported in CTE but have yet to be well characterized on a molecular or cellular level. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white matter from eight individuals with neuropathologically confirmed CTE and eight age- and sex-matched controls. Analyzing these profiles using unbiased clustering approaches, we identified eighteen transcriptomically distinct cell groups (clusters), reflecting cell types and/or cell states, of which a subset showed differences between CTE and control tissue. Independent in situ methods applied on tissue sections adjacent to that used in the single-nucleus RNA-seq work yielded similar findings. Oligodendrocytes were found to be most severely affected in the CTE white matter samples; they appeared diminished in number and altered in the relative proportions across subtype clusters. Further, the CTE-enriched oligodendrocyte population showed greater abundance of transcripts relevant to iron metabolism and cellular stress response. CTE tissue also demonstrated excessive iron accumulation histologically. Astrocyte alterations were more nuanced; total astrocyte number was indistinguishable between CTE and control samples, but transcripts associated with neuroinflammation were elevated in the CTE astrocyte groups as compared to controls. These results demonstrate specific molecular and cellular differences in CTE-associated oligodendrocytes and astrocytes and may provide a starting point for the development of diagnostics and therapeutic interventions.
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| Overall design |
Single-nucleus RNA sequencing comparative transcriptomic analysis of human subjects diagnosed neuropathologically with mid-state chronic traumatic encephalopathy (CTE) and age- and post-mortem (PMI)-matched controls.
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| Contributor(s) |
Chancellor KB, Okaty B, Dymecki SM |
| Citation(s) |
- Chancellor KB, Chancellor SE, Duke-Cohan JE, Huber BR et al. Altered oligodendroglia and astroglia in chronic traumatic encephalopathy. Acta Neuropathol 2021 Aug;142(2):295-321. PMID: 34019156
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| Submission date |
Jul 25, 2020 |
| Last update date |
Apr 04, 2023 |
| Contact name |
Kevin Blake Chancellor |
| E-mail(s) |
chancellor.kb@gmail.com
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| Organization name |
Harvard Medical School
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| Department |
Genetics
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| Lab |
Susan Dymecki
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| Street address |
77 Avenue Louis Pasteur
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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