Single-cell analysis identifies Ifi27l2a as a gene regulator of microglial inflammation in the context of aging and stroke in mice

被引：1

作者：

Kim, Gab Seok ^{[1
,2
]}

Harmon, Elisabeth ^{[1
,2
]}

Gutierrez, Manuel C. ^{[3
]}

Kim, Sodam ^{[1
,2
]}

Vance, Lauren ^{[1
,2
]}

Burrous, Haven ^{[1
,2
]}

Stephenson, Jessica M. ^{[1
]}

Chauhan, Anjali ^{[1
,2
]}

Banerjee, Anik ^{[1
,2
]}

Wise, Zachary ^{[1
]}

Doan, Andrea ^{[1
,2
]}

Ahn, John ^{[1
]}

Wu, Ting ^{[1
,2
]}

Bautista-Garrido, Jesus ^{[1
]}

Lee, Juneyoung ^{[1
,2
]}

Tan, Chunfeng ^{[1
,2
]}

Jung, Joo Eun ^{[1
]}

Mccullough, Louise D. ^{[1
,2
]}

Wythe, Joshua D. ^{[3
,4
,5
,6
,7
,8
]}

Marrelli, Sean P. ^{[1
,2
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Neurol, Houston, TX 77030 USA

[2] BRAINS Res Labs UTHlth, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Integrat Physiol, Houston, TX USA

[4] Baylor Coll Med, Dept Neurosurg, Houston, TX USA

[5] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA USA

[6] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA USA

[7] Univ Virginia, Brain Immunol & Glia BIG Ctr, Sch Med, Charlottesville, VA USA

[8] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Sch Med, Charlottesville, VA USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

关键词：

INTERFERON; MACROPHAGES; EXPRESSION; PROTECTS; INJURY;

D O I：

10.1038/s41467-025-56847-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inflammation is a significant driver of ischemic stroke pathology in the brain. To identify potential regulators of inflammation, we performed single-cell RNA sequencing (scRNA-seq) of young and aged mouse brains following stroke and found that interferon alpha-inducible protein 27 like 2 A (Ifi27l2a) was significantly up-regulated, particularly in microglia of aged brain. Ifi27l2a is induced by interferons for viral host defense and has been linked with pro-inflammatory cellular mechanisms. However, its potential role in neurodegeneration is unknown. Using a combination of cell culture, experimental stroke models in mice, and human autopsy brain samples, we demonstrated that induction of Ifi27l2a occurs in microglia in response to aging, ischemic stroke, and pro-inflammatory molecules. We further showed that induction of Ifi27l2a in microglia was sufficient to stimulate mitochondrial ROS production and promote a pro-inflammatory phenotype. Lastly, using an ischemic stroke model, we demonstrated that hemizygous deletion of Ifi27l2a (Ifi27l2a+/- mice) reduced gliosis (microgliosis and astrogliosis), acute and chronic brain injury, and motor function deficits. Together, these findings identify Ifi27l2a as a critical neuroinflammatory mediator in ischemic stroke and provide support for the therapeutic strategy of disrupting Ifi27l2a to attenuate inflammation in the post-stroke brain.

引用

页数：14

共 40 条

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