The Library
Epigenetic priming of immune/inflammatory pathways activation and abnormal activity of cell cycle pathway in a perinatal model of white matter injury
Tools
Tools
Tools
Schang, Anne-Laure, Van Steenwinckel, Juliette, Ioannidou, Zoi S., Lipecki, Julia, Rich-Griffin, Charlotte, Woolley-Allen, Kate, Dyer, Nigel P., Le Charpentier, Tifenn, Schäfer, Patrick, Fleiss, Bobbi, Ott, Sascha, Sabéran-Djoneidi, Délara, Mezger, Valérie and Gressens, Pierre (2022) Epigenetic priming of immune/inflammatory pathways activation and abnormal activity of cell cycle pathway in a perinatal model of white matter injury. Cell Death & Disease, 13 (12). 1038. doi:10.1038/s41419-022-05483-4 ISSN 2041-4889.
|
PDF
s41419-022-05483-4.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (7Mb) | Preview |
Official URL: https://doi.org/10.1038/s41419-022-05483-4
Abstract
Prenatal inflammatory insults accompany prematurity and provoke diffuse white matter injury (DWMI), which is associated with increased risk of neurodevelopmental pathologies, including autism spectrum disorders. DWMI results from maturation arrest of oligodendrocyte precursor cells (OPCs), a process that is poorly understood. Here, by using a validated mouse model of OPC maturation blockade, we provide the genome-wide ID card of the effects of neuroinflammation on OPCs that reveals the architecture of global cell fate issues underlining their maturation blockade. First, we find that, in OPCs, neuroinflammation takes advantage of a primed epigenomic landscape and induces abnormal overexpression of genes of the immune/inflammatory pathways: these genes strikingly exhibit accessible chromatin conformation in uninflamed OPCs, which correlates with their developmental, stage-dependent expression, along their normal maturation trajectory, as well as their abnormal upregulation upon neuroinflammation. Consistently, we observe the positioning on DNA of key transcription factors of the immune/inflammatory pathways (IRFs, NFkB), in both unstressed and inflamed OPCs. Second, we show that, in addition to the general perturbation of the myelination program, neuroinflammation counteracts the physiological downregulation of the cell cycle pathway in maturing OPCs. Neuroinflammation therefore perturbs cell identity in maturing OPCs, in a global manner. Moreover, based on our unraveling of the activity of genes of the immune/inflammatory pathways in prenatal uninflamed OPCs, the mere suppression of these proinflammatory mediators, as currently proposed in the field, may not be considered as a valid neurotherapeutic strategy.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RJ Pediatrics |
||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Encephalitis, Premature infants -- Diseases, Oligodendroglia | ||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Cell Death & Disease | ||||||||||||||||||||||||||||||||||||||||||
| Publisher: | Springer Nature | ||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 2041-4889 | ||||||||||||||||||||||||||||||||||||||||||
| Official Date: | 13 December 2022 | ||||||||||||||||||||||||||||||||||||||||||
| Dates: |
|
||||||||||||||||||||||||||||||||||||||||||
| Volume: | 13 | ||||||||||||||||||||||||||||||||||||||||||
| Number: | 12 | ||||||||||||||||||||||||||||||||||||||||||
| Article Number: | 1038 | ||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1038/s41419-022-05483-4 | ||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 6 February 2023 | ||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 6 February 2023 | ||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
