Identification of proliferating cardiogenic progenitors in the adult human ventricular subepicardial niche

July 6
Continuous adult myocardial renewal is critical for sustaining contractile performance and facilitating repair after injury, yet its existence in humans has been difficult to establish. Persistent challenges in detecting bona fide proliferative progenitor cells have raised questions about whether and how new cardiomyocytes are produced. We profiled human ventricular tissue from birth through adulthood using single-nucleus RNA sequencing. All stages of cardiogenic progenitors were readily observed in early childhood. In adult hearts, application of antibodies against the proliferation marker Ki67 combined with machine-learning–based image analysis revealed rare but unmistakable populations of dividing cardiogenic progenitor cells. Transcriptomic mapping further localized these progenitors to a discrete subepicardial domain of the left ventricle. These findings provide direct evidence for cardiomyocyte renewal in adult humans and delineate a spatially restricted niche that could be targeted for regenerative therapies.