The Jackson Laboratory, Bar Harbor, ME 04609, USA.
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Cell Rep. 2020 Mar 3;30(9):3149-3163.e6. doi: 10.1016/j.celrep.2020.02.008.
Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underlying scar formation, here we perform unbiased single-cell mRNA sequencing of interstitial cells isolated from infarcted mouse hearts carrying a genetic tracer that labels epicardial-derived cells. Sixteen interstitial cell clusters are revealed, five of which were of epicardial origin. Focusing on stromal cells, we define 11 sub-clusters, including diverse cell states of epicardial- and endocardial-derived fibroblasts. Comparing transcript profiles from post-infarction hearts in C57BL/6J and 129S1/SvImJ inbred mice, which displays a marked divergence in the frequency of cardiac rupture, uncovers an early increase in activated myofibroblasts, enhanced collagen deposition, and persistent acute phase response in 129S1/SvImJ mouse hearts, defining a crucial time window of pathological remodeling that predicts disease outcome.
心肌缺血导致心肌组织丧失，并激活修复过程，最终形成瘢痕，其结构特征决定了有利于愈合还是有害于心脏壁破裂的倾向。为了阐明瘢痕形成的细胞过程，我们在这里对携带标记心外膜细胞遗传示踪剂的梗死小鼠心脏分离的间质细胞进行了无偏单细胞 mRNA 测序。揭示了 16 个间质细胞簇，其中 5 个来自心外膜。我们专注于基质细胞，定义了 11 个亚簇，包括心外膜和心内膜来源成纤维细胞的多种细胞状态。比较 C57BL/6J 和 129S1/SvImJ 近交系小鼠梗死后心脏的转录谱，后者心脏破裂的频率明显不同，揭示了激活的肌成纤维细胞的早期增加、胶原沉积增强和 129S1/SvImJ 小鼠心脏中持续的急性期反应，定义了预测疾病结局的关键病理重塑时间窗口。
