Single-cell analysis identifies Ifi27l2a as a novel gene regulator of microglial inflammation in the context of aging and stroke.
Res Sq
; 2023 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-36824976
ABSTRACT
Microglia are key mediators of inflammatory responses within the brain, as they regulate pro-inflammatory responses while also limiting neuroinflammation via reparative phagocytosis. Thus, identifying genes that modulate microglial function may reveal novel therapeutic interventions for promoting better outcomes in diseases featuring extensive inflammation, such as stroke. To facilitate identification of potential mediators of inflammation, we performed single-cell RNA sequencing of aged mouse brains following stroke and found that Ifi27l2a was significantly up-regulated, particularly in microglia. The increased Ifi27l2a expression was further validated in microglial culture, stroke models with microglial depletion, and human autopsy samples. Ifi27l2a is known to be induced by interferons for viral host defense, however the role of Ifi27l2a in neurodegeneration is unknown. In vitro studies in cultured microglia demonstrated that Ifi27l2a overexpression causes neuroinflammation via reactive oxygen species. Interestingly, hemizygous deletion of Ifi27l2a significantly reduced gliosis in the thalamus following stroke, while also reducing neuroinflammation, indicating Ifi27l2a gene dosage is a critical mediator of neuroinflammation in ischemic stroke. Collectively, this study demonstrates that a novel gene, Ifi27l2a, regulates microglial function and neuroinflammation in the aged brain and following stroke. These findings suggest that Ifi27l2a may be a novel target for conferring cerebral protection post-stroke.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Res Sq
Año:
2023
Tipo del documento:
Article