Transcriptomic Analysis Identifies Transient Mesendodermal State and Lineage Divergence in Human Pluripotent Stem Cell Differentiation

Here we combined directed differentiation of human induced pluripotent stem cells toward neuroectodermal, cardiac mesodermal, and hepatic endodermal lineages with comparative transcriptomic profiling across timepoints.

Our analyses revealed a transient primitive streak-like mesendodermal state shared by mesodermal and endodermal trajectories, followed by lineage-specific divergence characterized by distinct transcriptional, metabolic, proliferative, and chromatin remodeling dynamics. Notably, endodermal differentiation exhibited rapid definitive endoderm commitment with enriched oxidative metabolism, whereas cardiac mesoderm differentiation showed progressive transcriptional remodeling and cardiac progenitor activation.