Multilineage contribution of CD34+ cells in cardiac remodeling after ischemia/reperfusion injury

This study aimed to delineate the biological functions of heterogenous CD34+ cell populations and investigate the net effect of CD34+ cell intervention on cardiac remodeling. We confirmed, by combining single-cell RNA sequencing on human and mouse ischemic hearts and an inducibleCd34 lineage-tracing mouse model, thatCd34+ cells mainly contributed to the commitment of mesenchymal cells, endothelial cells (ECs), and monocytes/macrophages during heart remodeling with distinct pathological functions. TheCd34+-lineage-activated mesenchymal cells were responsible for cardiac fibrosis, while CD34+Sca-1high was an active precursor and intercellular player that facilitatedCd34+-lineage angiogenic EC-induced postinjury vessel development. We found through bone marrow transplantation that bone marrow-derived CD34+ cells only accounted for inflammatory response. We confirmed using aCd34-CreERT2; R26-DTA mouse model that the depletion ofCd34+ cells could alleviate the severity of ventricular fibrosis after ischemia/reperfusion (I/R) injury with improved cardiac function. This study provided a transcriptional and cellular landscape of CD34+ cells in normal and ischemic hearts and illustrated that the heterogeneous population ofCd34+ cell-derived cells served as crucial contributors to cardiac remodeling and function after the I/R injury, with their capacity to generate diverse cellular lineages.
Source: Basic Research in Cardiology - Category: Cardiology Source Type: research