• Defined early lineage bifurcations (e.g., Mesp1 subsets for endocardium vs. myocardium).• Discovered transitional cell states (e.g., migrating SHF progenitors, cushion pre-EMT cells).• Linked specific transcription factors to lineage outcomes (e.g., Hand2 to OFT myocardium; Pitx2 to SHF lineage timing).• Uncovered gene expression changes in CHD models at single-cell level (e.g., mutant vs. wild-type differences). Here, HAND2 is linked to coronary artery disorder.