Single cell RNA-seq of neonatal heart regeneration

The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. Neonatal heart regeneration is orchestrated by multiple cell types intrinsic to the heart, as well as immune cells that infiltrate the heart after injury. To elucidate the transcriptional responses of the different cellular components of the mouse heart following injury, we performed single cell RNA-sequencing on neonatal hearts at various time points following myocardial infarction, and coupled the results with bulk tissue RNA-sequencing data collected at the same time points. Concomitant single cell ATAC-sequencing exposed underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types, and revealed previously unknown mediators of cardiomyocyte proliferation, angiogenesis and fibroblast activation. Together, our data provide a transcriptional basis for neonatal heart regeneration at single cell resolution and suggest new strategies for enhancing cardiac function in response to injury.

成年哺乳动物心脏损伤后再生能力有限，而新生心脏可在出生后短期内高效实现再生。新生心脏的再生过程由心脏固有多种细胞类型，以及损伤后浸润心脏的免疫细胞共同调控。为阐明小鼠心脏损伤后不同细胞组分的转录应答特征，本研究对心肌梗死（myocardial infarction）术后不同时间点的新生小鼠心脏开展单细胞RNA测序（single cell RNA-sequencing），并将测序结果与相同时间点采集的批量组织RNA测序（bulk tissue RNA-sequencing）数据进行整合分析。同步开展的单细胞ATAC测序（single cell ATAC-sequencing）揭示了多种心脏细胞类型的开放染色质景观动态变化与再生性基因调控网络，并发现了此前未被报道的心肌细胞增殖、血管生成及成纤维细胞活化调控介质。综上，本研究的数据以单细胞分辨率为新生心脏再生提供了转录组学基础，并为损伤后改善心脏功能提出了全新干预策略。