Single-cell transcriptomics of human traumatic brain injury reveals activation of endogenous retroviruses in oligodendroglia
(2023) In Cell Reports 42(11).- Abstract
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... (More)
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.
(Less)
- author
- organization
-
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Molecular Neurogenetics (research group)
- Wallenberg Neuroscience Centre, Lund
- Stem Cell Center
- Developmental and Regenerative Neurobiology (research group)
- Pathology, Lund
- WCMM-Wallenberg Centre for Molecular Medicine
- Human Neural Developmental Biology (research group)
- LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research (research group)
- Neurosurgery
- publishing date
- 2023-11-08
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Reports
- volume
- 42
- issue
- 11
- article number
- 113395
- publisher
- Cell Press
- external identifiers
-
- scopus:85178228560
- pmid:37967557
- ISSN
- 2211-1247
- DOI
- 10.1016/j.celrep.2023.113395
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
- id
- 13d28144-8a1c-4ff3-9bc4-48459e764be0
- date added to LUP
- 2023-11-17 14:37:19
- date last changed
- 2024-09-05 23:43:32
@article{13d28144-8a1c-4ff3-9bc4-48459e764be0, abstract = {{<p>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.</p>}}, author = {{Garza, Raquel and Sharma, Yogita and Atacho, Diahann A M and Thiruvalluvan, Arun and Abu Hamdeh, Sami and Jönsson, Marie E and Horvath, Vivien and Adami, Anita and Ingelsson, Martin and Jern, Patric and Hammell, Molly Gale and Englund, Elisabet and Kirkeby, Agnete and Jakobsson, Johan and Marklund, Niklas}}, issn = {{2211-1247}}, language = {{eng}}, month = {{11}}, number = {{11}}, publisher = {{Cell Press}}, series = {{Cell Reports}}, title = {{Single-cell transcriptomics of human traumatic brain injury reveals activation of endogenous retroviruses in oligodendroglia}}, url = {{http://dx.doi.org/10.1016/j.celrep.2023.113395}}, doi = {{10.1016/j.celrep.2023.113395}}, volume = {{42}}, year = {{2023}}, }