Heart failure & cardiomyopathies
The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft
Authors' conclusion
Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.
Study context
- Population
- Human pediatric cardiac allografts at different stages after transplantation
- Outcome
- Macrophage landscape (single-nucleus RNA sequencing, donor vs recipient origin)
Methodological detailsDonor- vs recipient-derived cells distinguished using naturally occurring genetic variants in single-nucleus RNA sequencing data
- Donor- vs recipient-derived cells distinguished using naturally occurring genetic variants in single-nucleus RNA sequencing data
Main finding
As reported in the abstract
- Donor-derived tissue resident macrophages are lost over time after transplantation
- Recipient monocyte-derived macrophages populate the heart within days and form 2 populations: recipient MP1 and recipient MP2
- Recipient MP2s resemble donor-derived resident macrophages but lack pro-reparative phagocytic signatures and express profibrotic genes
- Recipient MP1s express genes consistent with hallmarks of cellular rejection
- Recipient MP1s may activate a subset of natural killer cells into a cytotoxic population via feed-forward signaling
Original publication
The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft. Circulation. Published 12 February 2024. doi:10. 1161/ circulationaha. 123. 065294
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