“Single-Cell Transcriptomics of Resected Human Traumatic Brain Injury Tissues Reveals Acute Activation of Endogenous Retroviruses in Oligodendrocytes”, Raquel Garza, Yogita Sharma, Diahann Atacho, Sami Abu Hamdeh, Marie E. Jonsson, Martin Ingelsson, Patric Jern, Molly Gale Hammell, Elisabet Englund, Johan Jakobsson, Niklas Marklund2022-09-09 (TBI)⁠:

Traumatic brain injury (TBI) is a leading cause of persistent functional brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology.

Here, we used single-nuclei RNA-sequencing to study transcriptomic changes in different cell populations from human brain tissue obtained acutely after severe, life-threatening TBI.

We found a unique transcriptional response in several cell types, including the activation of an interferon response in oligodendrocytes coupled with the transcriptional activation of MHC-class I and class II related genes. Thus, oligodendrocytes undergo a transformation to an immune-like cell state immediately after TBI, indicating an important role for these cells in the initiation of neuroinflammation. Notably, the activation of immune-related genes correlated with the expression of endogenous retroviruses in oligodendrocytes, linking these ancient viral sequences to neuroinflammation.

In summary, this work provides a unique insight into the initiating events of the neuroinflammatory response in TBI, which has new therapeutic implications.