The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.

心脏干细胞（CSC）群体对于心脏再生的重要性仍然存在争议。在这里，我们应用干细胞功能的最直接定义（通过细胞分裂来替代失去的组织的能力）来询问CSC的存在。通过使用两个Ki67敲入小鼠模型的单细胞mRNA测序和遗传谱系追踪，我们绘制了在恒动和再生鼠心中所有增殖细胞及其后代的图谱。仅在出生后早期阶段就强烈观察到了循环心肌细胞，而在恒压和受损成年心肌中的循环细胞代表了各种非心肌细胞类型。表达卵泡抑素样蛋白1（FSTL1）的增生性损伤后成纤维细胞与新生儿心脏成纤维细胞非常相似，并形成纤维化瘢痕。基因缺失心脏成纤维细胞中的Fstl1会导致损伤后心脏破裂。我们没有证据表明存在静息的CSC群体，其他类型的细胞向心肌细胞转分化，或大量心肌细胞对心脏损伤的反应而增殖的证据。