Single-cell transcriptomics of resected human traumatic brain injury tissues reveals acute activation of endogenous retroviruses in oligodendrocytes
Garza, R. et al. (BioRxiv) doi: 10.1101/2022.09.07.506982

Keywords

  • Traumatic Brain Injury (TBI)

  • Endogenous Retrovirus (ERV)

  • Oligodendrocytes

  • Interferon

  • Human, snRNAseq

 

Main Findings

Traumatic Brain Injury (TBI) and the associated neuroinflammation can lead to long term impairment but remain poorly characterized. The authors used single-nuclei RNA-sequencing to study transcriptomic changes in different cell populations from human brain tissue(temporal and frontal lobe)obtained acutely after severe, life-threatening TBI.

Garza et al. show that oligodendrocytes in human samples post TBI initiate an interferon response as well as the expression of major histocompatibility complex (MHC) type I and II gene, suggesting the adoption of immune-like cell features. Concomitantly the interferon response correlates with ERV activation in Oligodendrocytes/OPC post TBI.

Limitations

  • The patient cohort was heterogenous with age range of+/-18.2 years. Also, the severe TBI was defined as GOCS above 8, which is a clinical definition based on symptoms and not on the inflammatory process that is ongoing.

  • The control group was older than TBI patients, which could also be seen as an advantage: age is in a general a more inflammatory state, and the inflammation induced changes post TBI hold up to this

  • It remains unclear how are ERVs activated in oligodendrocytes, and whether they directly impact inflammatory functions. Chicken and egg question: are ERVs driving or a consequence of neuroinflammation?

  • The preprint would benefit from afunctional assessment of the observed transcriptional/phenotypical changes.

Significance/Novelty

 

The strength of this preprint lays in the unique presentation of an upregulation of ERV containing open reading frames capable of producing proteins in oligodendrocytes from brain human samples post TBI. With their results, Garza et al. put oligodendrocytes on the map, as potential modulators of inflammation.

Credit

Reviewed by Susanne Neumann as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai (U.S.A.), the Kennedy Institute of Rheumatology, University of Oxford (U.K.), and the Center for Molecular Medicine, Karolinska Institutet (Sweden).