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Single-Nucleus Transcriptomics Identifies Microglial Interferon Regulatory Factor 5 as a Regulator of
Wanxin Tang1, Yang Yu1, Jing-Yu Bing2
1Department of Internal Medicine University of Iowa Iowa City IA USA.
Journal of the American Heart Association
|August 7, 2026
Summary
Heart failure activates microglia in the brain's paraventricular nucleus (PVN), a key autonomic center. This study identifies interferon regulatory factor 5 (IRF5) in microglia as a critical driver of neuroinflammation and sympathetic dysfunction.
Area of Science:
- Neuroscience
- Cardiovascular Biology
- Immunology
Background:
- The paraventricular nucleus (PVN) regulates autonomic and cardiovascular functions.
- Neuroinflammation in the PVN contributes to sympathetic overactivity in heart failure.
- Understanding cellular mechanisms in the PVN is crucial for heart failure progression.
Purpose of the Study:
- To define cellular and transcriptional mechanisms of inflammatory signaling in the PVN during heart failure.
- To investigate changes in the PVN using single-nucleus RNA sequencing (snRNA-seq) after myocardial infarction (MI).
Main Methods:
- Performed snRNA-seq on rat PVN 2 weeks post-MI.
- Analyzed sequencing data to identify cell populations and gene expression profiles.
- Utilized Gene Set Variation Analysis and regulatory network analyses to identify pathways and transcription factors.
Main Results:
- Classified 16,341 nuclei into 5 major cell types: neurons, oligodendrocytes, astrocytes, OPCs, and microglia.
- Identified microglia as primary mediators of inflammatory responses in the PVN.
- Found significant upregulation of immune-related pathways and IRF5 in PVN microglia of MI rats.
Conclusions:
- snRNA-seq revealed cell-specific signatures and pathways in the PVN during heart failure.
- Microglial IRF5 is a central regulator of immune activation and neuroinflammation in the PVN.
- Targeting IRF5 may offer therapeutic strategies for heart failure-related cardiac dysfunction.