Single cell RNA sequencing of non-cardiac myocyte cells isolated from wildtype and macrophage-specific miR-21 knockout mice hearts 6 days after TAC surgery.

Mice with macrophage-specific (Cx3cr1-Cre-mediated) genetic deletion of miR-21 (miR-21 cKO) were protected from interstitial fibrosis and cardiac dysfunction when subjected to pressure overload of the left ventricle. In order to better understand the mechanism through which miR-21 exerts its function in cardiac macrophages and how this then determines responses in other myocardial cell fractions, we carried out single cell sequencing using the non-myocyte cell population isolated from either WT or miR-21 cKO mice 6 days after pressure overload. Single cell sequencing revealed that miR-21 in macrophages is essential for their polarization towards a M1-like phenotype, and identified the cardiac fibroblast as the primary recipient cell of intercellular signals that emanate from activated cardiac macrophages and that are controlled by miR-21.