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Single-cell transcriptomics of human traumatic brain injury reveals activation of endogenous retroviruses in oligodendroglia

2023; Cell Press; Volume: 42; Issue: 11 Linguagem: Inglês

10.1016/j.celrep.2023.113395

2639-1856

Raquel Garza, Yogita Sharma, Diahann A. M. Atacho, Arun Thiruvalluvan, Sami Abu Hamdeh, Marie E. Jönsson, Vivien Horváth, Anita Adami, Martin Ingelsson, Patric Jern, Molly Hammell, Elisabet Englund, Agnete Kirkeby, Johan Jakobsson, Niklas Marklund,

Immune cells in cancer

Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used single-nuclei RNA sequencing (snRNA-seq) to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides insight into the initiating events of the neuroinflammatory response in TBI, which has therapeutic implications.