Fate-mapping infiltrating monocytes following experimental myocardial infarction revealsdifferentiation trajectories in the infarcted heart

Andrew L Koenig; Farid F Kadyrov; Junedh M Amrute; Steven Yang; Carla J Weinheimer; Jessica M Nigro; Attila Kovacs; Wenjun Li; Gabriella B Smith; Lance Yeh; Daniel Kreisel; Kory J Lavine

doi:10.1172/JCI189684

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Fate-mapping infiltrating monocytes following experimental myocardial infarction revealsdifferentiation trajectories in the infarcted heart

Journal article

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Fate-mapping infiltrating monocytes following experimental myocardial infarction revealsdifferentiation trajectories in the infarcted heart

Andrew L Koenig, Farid F Kadyrov, Junedh M Amrute, Steven Yang, Carla J Weinheimer, Jessica M Nigro, Attila Kovacs, Wenjun Li, Gabriella B Smith, Lance Yeh, …

The Journal of clinical investigation

07/07/2026

DOI: 10.1172/JCI189684

PMID: 42412552

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Abstract

Inflammation contributes to the pathogenesis of myocardial infarction and heart failure and represents a viable therapeutic target. Monocytes and their progeny are highly abundant and display striking functional diversity, serving as key determinants of myocardial inflammation and tissue repair. Much remains to be learned regarding mechanisms and signaling events that instruct monocyte fate decisions. We devised a genetic lineage tracing strategy using Ccr2crERT2Rosa26LSL-tdTomato mice in combination with single cell RNA-sequencing to map the differentiation trajectories of monocytes that infiltrate the heart after reperfused myocardial infarction. Monocytes were recruited to the heart early after injury and gave rise to transcriptionally distinct and spatially restricted macrophage and dendritic cell-like subsets that were specified prior to extravasation and chronically persisted within the myocardium. Pseudotime analysis predicted two differentiation trajectories of monocyte-derived macrophages that are partitioned into the border and infarct zones, respectively. Among these trajectories, we demonstrated that macrophages expressing a type I interferon responsive signature were an intermediate population that gave rise to MHC-IIhi macrophages, were localized within the border zone, induce regulatory T cells, and promote myocardial protection. Collectively, these data uncover complexities of monocyte differentiation in the infarcted heart and suggest that modulating monocyte fate decisions may have clinical implications.

Cardiology

Heart Failure

Immunology

Macrophages

Cellular immune response

Details

Title: Subtitle: Fate-mapping infiltrating monocytes following experimental myocardial infarction revealsdifferentiation trajectories in the infarcted heart
Creators: Andrew L Koenig - Washington University in St. Louis
Farid F Kadyrov - Washington University in St. Louis
Junedh M Amrute - Washington University in St. Louis
Steven Yang - Washington University in St. Louis
Carla J Weinheimer - Washington University in St. Louis School of Medicine
Jessica M Nigro - Washington University in St. Louis
Attila Kovacs - Washington University in St. Louis
Wenjun Li - Washington University in St. Louis School of Medicine
Gabriella B Smith - Washington University in St. Louis
Lance Yeh - Washington University in St. Louis
Daniel Kreisel - Washington University in St. Louis
Kory J Lavine - Washington University in St. Louis
Resource Type: Journal article
Publication Details: The Journal of clinical investigation
DOI: 10.1172/JCI189684
PMID: 42412552
NLM abbreviation: J Clin Invest
ISSN: 1558-8238
eISSN: 1558-8238
Publisher: American Society for Clinical Investigation
Language: English
Electronic publication date: 07/07/2026
Academic Unit: Cardiology; Stead Family Department of Pediatrics
Record Identifier: 9985180875902771

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