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中国科学院分子细胞科学卓越创新中心周斌团队利用双重遗传追踪揭示调节心脏纤维化的独特成纤维细胞亚群。2023年3月23日，《自然—遗传学》杂志在线发表了这项成果。

研究人员使用双重组酶介导的遗传谱系追踪，发现心内膜衍生的成纤维细胞在压力过载的情况下优先增殖和扩张。成纤维细胞特异性增殖追踪显示，受伤后激活的成纤维细胞高度区域性扩张，其模式反映了心内膜衍生的成纤维细胞在心脏中的分布。心内膜源性成纤维细胞的特异性去除可以缓解心脏纤维化，并减少压力过载损伤后心脏功能的下降。从机制上讲，Wnt信号促进了心脏重塑过程中心内膜来源成纤维细胞的激活和扩张。这项研究发现，心内膜源性成纤维细胞是压力过载损伤后严重心脏纤维化的关键成纤维细胞亚群，也是对抗心脏纤维化的潜在治疗靶点。

据悉，严重的心脏损伤后，成纤维细胞被激活并过度增殖，形成瘢痕，导致心脏功能下降，并最终导致心力衰竭。然而，心脏成纤维细胞在心脏纤维化过程中的激活程度、增殖和功能方面是否具有异质性尚不清楚。

附：英文原文

Title: Dual genetic tracing reveals a unique fibroblast subpopulation modulating cardiac fibrosis

Author: Han, Maoying, Liu, Zixin, Liu, Lei, Huang, Xiuzhen, Wang, Haixiao, Pu, Wenjuan, Wang, Enci, Liu, Xiuxiu, Li, Yan, He, Lingjuan, Li, Xufeng, Wu, Jiayu, Qiu, Lin, Shen, Ruling, Wang, Qing-Dong, Ji, Yong, Ardehali, Reza, Shu, Qiang, Lui, Kathy O., Wang, Lixin, Zhou, Bin

Issue&Volume: 2023-03-23

Abstract: After severe heart injury, fibroblasts are activated and proliferate excessively to form scarring, leading to decreased cardiac function and eventually heart failure. It is unknown, however, whether cardiac fibroblasts are heterogeneous with respect to their degree of activation, proliferation and function during cardiac fibrosis. Here, using dual recombinase-mediated genetic lineage tracing, we find that endocardium-derived fibroblasts preferentially proliferate and expand in response to pressure overload. Fibroblast-specific proliferation tracing revealed highly regional expansion of activated fibroblasts after injury, whose pattern mirrors that of endocardium-derived fibroblast distribution in the heart. Specific ablation of endocardium-derived fibroblasts alleviates cardiac fibrosis and reduces the decline of heart function after pressure overload injury. Mechanistically, Wnt signaling promotes activation and expansion of endocardium-derived fibroblasts during cardiac remodeling. Our study identifies endocardium-derived fibroblasts as a key fibroblast subpopulation accounting for severe cardiac fibrosis after pressure overload injury and as a potential therapeutic target against cardiac fibrosis.

DOI: 10.1038/s41588-023-01337-7

Source: https://www.nature.com/articles/s41588-023-01337-7

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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