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

Garza, Raquel LU orcid ; Sharma, Yogita LU ; Atacho, Diahann A M LU orcid ; Thiruvalluvan, Arun ; Abu Hamdeh, Sami ; Jönsson, Marie E LU ; Horvath, Vivien LU orcid ; Adami, Anita LU ; Ingelsson, Martin and Jern, Patric , et al. (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.

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organization
publishing date
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
2024-04-17 11:21:39
@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}},
}