Cross-species single-cell comparison of systemic and cardiac inflammatory responses after cardiac injury.
Cross-species single-cell comparison of systemic and cardiac inflammatory responses after cardiac injury.
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心脏损伤后全身和心脏炎症反应的跨物种单细胞比较。
DOI：
10.1101/2023.03.15.532865
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lo,JamesC
中科院分区：
文献类型：
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作者：
Cortada,Eric;Yao,Jun;Xia,Yu;Dündar,Friederike;Zumbo,Paul;Yang,Boris;Rubio-Navarro,Alfonso;Perder,Björn;Qiu,Miaoyan;Pettinato,AnthonyM;Homan,EdwinA;Stoll,Lisa;Betel,Doron;Cao,Jingli;Lo,JamesC
免疫系统协调对心脏损伤的反应，并且已知控制心脏中的再生和纤维化瘢痕结果以及随后与心力衰竭相关的慢性低度炎症。在这里，我们使用单细胞转录组学来分析心脏损伤的炎症反应，以比较和对比两种具有不同结果的实验模型。我们使用了成年小鼠，它们像人类一样缺乏完全恢复的能力，而斑马鱼在心脏损伤后自发再生。还询问了对心肌细胞坏死的心外反应，以评估特定的外周组织和免疫细胞对慢性应激的反应。已知心脏巨噬细胞在通过愈合与瘢痕形成来确定组织稳态中起关键作用。我们在每个物种中鉴定了单核细胞/巨噬细胞的不同转录簇，并在斑马鱼和小鼠中发现了类似的对。然而，小鼠和斑马鱼对心肌损伤的反应在很大程度上是不同的。哺乳动物和斑马鱼单核细胞/巨噬细胞对心脏损伤的二分反应可能是小鼠再生过程受损的基础，代表了未来的治疗靶点。
The immune system coordinates the response to cardiac injury and is known to control regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Here we profiled the inflammatory response to heart injury using single cell transcriptomics to compare and contrast two experimental models with disparate outcomes. We used adult mice, which like humans lack the ability to fully recover and zebrafish which spontaneously regenerate after heart injury. The extracardiac reaction to cardiomyocyte necrosis was also interrogated to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages are known to play a critical role in determining tissue homeostasis by healing versus scarring. We identified distinct transcriptional clusters of monocytes/macrophages in each species and found analogous pairs in zebrafish and mice. However, the reaction to myocardial injury was largely disparate between mice and zebrafish. The dichotomous response to heart damage between the mammalian and zebrafish monocytes/macrophages may underlie the impaired regenerative process in mice, representing a future therapeutic target.