ArticleNature communications2025
Single-cell analysis identifies Ifi27l2a as a gene regulator of microglial inflammation in the context of aging and stroke in mice.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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41 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Histological Insights into the Neuroprotective Effects of Antioxidant Peptides and Small Molecules in Cerebral Ischemia.Molecules (Basel, Switzerland) · 2025Pooled it
- Neurotoxicity, α-synuclein pathology, and mitochondrial dysfunction: A comparative study of different mouse models of Parkinson's disease.Neural regeneration research · 2026Article
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- Analytical Methods and Application of Single-Cell and Single-Nucleus Transcriptomics in the Study of Ischemic Stroke.Biomolecules · 2026Review
- Multi-Omics Integration in Stroke: Neuroinflammatory Endotypes, Immune Cell Crosstalk, and Precision Biomarker Discovery.International journal of molecular sciences · 2026Review
- Microglial IRF7-induced lipophagy impairment aggravates lipid droplet overload and impedes neurological recovery after ischemic stroke.Journal of neuroinflammation · 2026Article
- Shared transcriptomic signatures in perilesional and contralesional cortex after ischemic stroke.Journal of neuroinflammation · 2026Article
- Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging.Nature communications · 2026Article
- Lysophosphatidic Acid Reduces Ischemic Brain Injury by Attenuating Vascular Permeability Through LPA4 Receptor Signaling.Translational stroke research · 2026Article
- Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Ammonia Detoxification Inhibits Liver Metastasis by Reshaping Hepatic Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Comparative analysis of clearing methods for 3D imaging of the vasculature in mineralized mouse tissues.iScience · 2026Article
- A multi-omic atlas in the African turquoise killifish reveals increased glucocorticoid signaling as a hallmark of brain aging.bioRxiv : the preprint server for biology · 2026Article
- Circadian Rhythm Disorder-Related Dysfunctions are Exacerbated by Aging and Ameliorated by Time-Restricted Feeding.Neuroscience bulletin · 2026Article
- Sex-specific hypothalamic PVN transcriptomic signatures of blood pressure autonomic regulation and neuroinflammation in hypertension.Biology of sex differences · 2026Article
- Shared Transcriptomic Signatures in Perilesional and Contralesional Cortex.bioRxiv : the preprint server for biology · 2026Article
- Distinct Endothelial Phenotype Associates with Macrophage-Enriched Microenvironments in Triple-Negative Breast Cancer.Research square · 2026Article
- Silencing of Ifi27l2a Attenuates Inflammation After Spinal Cord Injury by Regulating Microglial Polarization via JAK2/STAT3 Signaling.Molecular neurobiology · 2026Article
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
- Single-cell and single-nucleus transcriptomics in ischemic stroke: cellular mechanisms and therapeutic implications.Frontiers in neurology · 2026Review
Corrections and comments
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Authors and funding
20 authors.
Gab Seok KimDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Gab.Kim@uth.tmc.edu.
Elisabeth HarmonDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Manuel C GutierrezDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Sodam KimDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Lauren VanceDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Haven BurrousDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jessica M StephensonDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Anjali ChauhanDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9825-8100
Anik BanerjeeDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Zachary WiseDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Andrea DoanDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
John AhnDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Ting WuDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jesus Bautista-GarridoDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5041-5293
Juneyoung LeeDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Chunfeng TanDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7083-1529
Joo Eun JungDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Louise D McCulloughDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8050-1686
Joshua D WytheDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Sean P MarrelliDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Sean.P.Marrelli@uth.tmc.edu.
Funding
Modifying endothelial Piezo 1 function to improve brain perfusion in AD/ADRDR01AG081942 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Sean P Marrelli · 2023 to 2026
$2.7MDecoding the Molecular and Cellular Mechanisms of Mutant KRAS-driven Brain Arteriovenous MalformationsR01HL159159 · NHLBI · UNIVERSITY OF VIRGINIA · PI WYTHE, JOSHUA D. · 2022 to 2025
$2.6MIfi27l2a as a therapeutic target for strokeR01NS133324 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI GAB SEOK KIM · 2023 to 2026
$1.9MDefining the role of endothelial Piezo1, a mechanosensitive ion channel, in providing resilience to vascular contributions to cognitive impairment and dementia (VCID)R56NS120709 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MARRELLI, SEAN P · 2021 to 2021
$620kTargeting intramural von Willebrand factor (VWF) to improve vasomotor function, enhance brain parenchymal clearance, & delay development of cerebral amyloid angiopathy (CAA) in conditions of amyloidR56AG084130 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MARRELLI, SEAN P · 2023 to 2023
$619kEnhancing microglia-dependent plaque clearance in the Alzheimer disease brain by targeting Ifi27l2a expressionR21AG072488 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KIM, GAB SEOK · 2021 to 2021
$429kSkyScan 1276: Multiscale Micro-CT SystemLaboratory S10OD030336 · OD · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MARRELLI, SEAN P · 2021 to 2021
$368kNHLBI NIH HHS R01 HL159159NIA NIH HHS R01 AG081942NIA NIH HHS R21 AG072488NIA NIH HHS R56 AG084130NIH HHS S10 OD030336NINDS NIH HHS R01 NS133324NINDS NIH HHS R56 NS120709U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL159159U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS133324U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG081942U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R21AG072488U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R56AG084130U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R56NS120709
Abstract
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
Indexed as
AgingInflammationMicrogliaMitochondrial ProteinsStrokeAnimalsBrainDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaReactive Oxygen SpeciesMitochondrial ProteinsReactive Oxygen Species
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