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

Autor:	Garza R; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Sharma Y; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Atacho DAM; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Thiruvalluvan A; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) and Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark., Abu Hamdeh S; Department of Neuroscience, Neurosurgery, Uppsala University, Uppsala, Sweden., Jönsson ME; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Horvath V; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Adami A; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Ingelsson M; Department of Public Health and Caring Sciences, Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Krembil Brain Institute, University Health Network, Toronto, ON, Canada., Jern P; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Hammell MG; Institute for Systems Genetics, Department of Neuroscience and Physiology, NYU Langone Health, New York, NY 10016, USA; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10003, USA., Englund E; Department of Clinical Sciences Lund, Division of Pathology, Lund University, Lund, Sweden., Kirkeby A; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) and Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark; Department of Experimental Medical Science, Wallenberg Center for Molecular Medicine and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden., Jakobsson J; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden. Electronic address: johan.jakobsson@med.lu.se., Marklund N; Department of Clinical Sciences Lund, Neurosurgery, Lund University, Skåne University Hospital, Lund, Sweden.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Nov 28; Vol. 42 (11), pp. 113395. Date of Electronic Publication: 2023 Nov 14.
DOI:	10.1016/j.celrep.2023.113395
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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