A transient wave of Bhlhe41+ resident macrophages enables remodeling of the developing infarcted myocardium
Yue Xu,
Kai Jiang,
Fanghua Su,
Ruhua Deng,
Zhiyang Cheng,
Dandan Wang,
Yong Yu,
Yaozu Xiang
Affiliations
Yue Xu
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Kai Jiang
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Fanghua Su
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Ruhua Deng
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Zhiyang Cheng
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Dandan Wang
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Yong Yu
Department of Hematology, Tongji Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Yaozu Xiang
Shanghai East Hospital, Key Laboratory of Arrhythmias of the Ministry of Education of China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Corresponding author
Summary: The immune system plays a critical role during myocardial injury, contributing to repair and remodeling post myocardial infarction (MI). The myocardial infarct and border zone exhibit high heterogeneity, in turn leading to reconstructing macrophage subsets and specific functions. Here we use a combination of single-cell RNA sequencing, spatial transcriptomes, and reporter mice to characterize temporal-spatial dynamics of cardiac macrophage subtype in response to MI. We identify that transient appearance of monocyte-derived Bhlhe41+ Mφs in the “developing” infarct zone peaked at day 7, while other monocyte-derived macrophages are identified in “old” infarct zone. Functional characterization by co-culture of Bhlhe41+ Mφs with cardiomyocytes and fibroblasts or depletion of Bhlhe41+ Mφs unveils a crucial contribution of Bhlhe41+ Mφs in suppression of myofibroblast activation. This work highlights the importance of Bhlhe41+ Mφ phenotype and plasticity in preventing excessive fibrosis and limiting the expansion of developing infarct area.
