Department of Molecular Biology, The Hamon Center for Regenerative Science and Medicine, and Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Department of Molecular Biology, The Hamon Center for Regenerative Science and Medicine, and Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Cell Rep. 2020 Dec 8;33(10):108472. doi: 10.1016/j.celrep.2020.108472.
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 perform single-cell RNA sequencing on neonatal hearts at various time points following myocardial infarction and couple the results with bulk tissue RNA-sequencing data collected at the same time points. Concomitant single-cell ATAC sequencing exposes underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types and reveals extracellular 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 strategies for enhancing cardiac function after injury.
成年哺乳动物的心脏在受伤后再生能力有限，而新生动物的心脏在出生后很短的时间内就能很容易地再生。新生儿心脏的再生是由心脏内的多种细胞类型以及受伤后浸润心脏的免疫细胞共同协调的。为了阐明损伤后小鼠心脏不同细胞成分的转录反应，我们对心肌梗死发生后不同时间点的新生鼠心脏进行单细胞 RNA 测序，并将结果与同时收集的大量组织 RNA 测序数据进行关联。伴随的单细胞 ATAC 测序揭示了不同心脏细胞类型的开放染色质景观和再生基因调控网络的潜在动态，并揭示了心肌细胞增殖、血管生成和成纤维细胞激活的细胞外介质。总之，我们的数据为单细胞分辨率下的新生儿心脏再生提供了转录基础，并为损伤后增强心脏功能提供了策略。
