Multicellular Transcriptional Analysis of Mammalian Heart Regeneration

The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes.

成年哺乳动物心脏在损伤后无法再生，是心血管医学领域面临的一大核心障碍。与之相反，新生哺乳动物心脏则拥有一过性的再生能力，该能力在出生后不久便会丧失。阐明新生期心脏再生能力的调控分子机制，仍是心脏生物学领域的核心研究目标之一。本研究首次构建了多类心脏细胞群的转录组图谱，得以实现再生状态（新生期）与非再生状态（成年期）的对比分析。本研究为心脏发育、修复及再生过程中的多类心脏细胞群提供了一套全面的转录组研究资源。本研究结果明确了支撑新生期心脏再生状态的转录程序，并鉴定出成年心肌细胞中重新激活该再生程序所面临的表观遗传屏障。