Abstract
Identifying lineage‐specific markers is pivotal for understanding developmental processes and developing cell therapies. We report a new cardiac‐specific cell surface marker, latrophilin 2 (LPHN2), expressed specifically by cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during mouse and human pluripotent stem cells (PSCs) differentiation in vitro and exclusively in the heart during mouse embryonic development. Lphn2 knockout in mice is embryonically lethal owing to severe heart, but not vascular, defects. PSC‐ derived LPHN2 cells differentiated into CMCs and regenerated the myocardium when transplanted into the infarcted heart, unlike LPHN2‐ cells. Transplanted LPHN2 cells improved left‐ventricle systolic function and reduced infarct size. Molecular pathway analysis showed that CDK5 was a key downstream molecule of LPHN2 that interacted in parallel with Src and induced P38MAPK phosphorylation, subsequently activating cardiac‐related gene transcription. These findings provide a valuable tool for isolating cardiomyogenic progenitors and CMCs from PSCs and shed light on heart development and regeneration.
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