Intercellular genetic tracing of cardiac endothelium in the developing heart.

Cardiac resident macrophages play vital roles in heart development, homeostasis, repair, and regeneration. Recent studies documented the hematopoietic potential of cardiac endothelium that supports the generation of cardiac macrophages and peripheral blood cells in mice. However, the conclusion was not strongly supported by previous genetic tracing studies, given the non-specific nature of conventional Cre- loxP tracing tools. Here, we develop an intercellular genetic labeling system that can permanently trace heart-specific endothelial cells based on cell-cell interaction in mice. Results from cell-cell contact-mediated genetic fate mapping demonstrate that cardiac endothelial cells do not exhibit hemogenic potential and do not contribute to cardiac macrophages or other circulating blood cells. This Matters Arising paper is in response to Shigeta et al. (2019), published in Developmental Cell. See also the response by Liu and Nakano (2023), published in this issue. [Display omitted] • Generation of intercellular genetic recording system to label neighboring cells • Genetic tracing of endocardium and coronary endothelial cells by cell-cell contact • Cardiac endothelium does not have hematopoietic potential in development • Cell-cell contact-mediated labeling enhances the specificity of genetic tracing In this Matters Arising article, Liu and Jin et al. re-evaluate the model that the developing endocardium is hemogenic and generates cardiac macrophages and circulating blood cells, which was proposed by Shigeta et al. By using an intercellular genetic tracing system that enables specific labeling of cardiac endothelium, they find that the cardiac endothelium does not have hematopoietic activity during heart development. [ABSTRACT FROM AUTHOR]