Single-cell and spatial transcriptomic analyses reveals the dynamic transcript profiles of myocardial lymphangiogenesis post-myocardial infarction

Abstract Background: Cardiac lymphatics play an important role in myocardial edema and inflammation, however, the heterogeneity of cardiac lymphatic endothelial cells (LECs) and their biological functions have rarely been investigated. Methods: This study integrated single-cell sequencing data and spatial transcriptome data from mouse heart tissue at different time points post-myocardial infarction (MI), and then revealed LECs heterogeneity and biological functions by clustering, spatial localization, cell trajectory, and Cell-Chat analyses. Results: Four transcriptionally distinct subtypes of LECs were identified and localized in space. Cardiac LEC subgroups were found to be localized in different zones of infarcted heart related to different functions. LEC capillary III (LEC CaIII) may be involved in the direct regulation of myocardial injuries in an infarcted zone (IZ) from the perspective of metabolic stress, while LEC CaII may be related to the rapid immune inflammatory responses of the border zone (BZ) in the early stage of MI. LEC CaI, as well as LEC collection mainly participate in the regulation of myocardial tissue edema resolution in the middle and late stages post-MI. Cell trajectory and Cell-Chat analyses further identified that LECs may regulate myocardial edema through Aquaporin 1, and might affect the infiltration of macrophages through the galectin-9 (Gal-9)-CD44 pathway. Conclusion: This study revealed the dynamic transcriptional heterogeneity distribution of LECs in different regions of the infarcted heart, and these LECs formed different functional subgroups that might exhibit different bioeffects in myocardial tissue post-MI.