Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.
M, Z., C, L., R, K., X, W., Y, Y., D, W., Z, A., B, N., Z, L., & T, L. (2026). Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.. Science advances. https://doi.org/10.1126/sciadv.aee5316
M Z, C L, R K, X W, Y Y, D W, et al. Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.. Science advances. 2026; doi: 10.1126/sciadv.aee5316
M Z, C L, R K, et al. Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.[J]. Science advances. 2026. DOI: 10.1126/sciadv.aee5316.
@article{m2026,
author = {Zhou M and Li C and Kong R and Wang X and Yin Y and Wang D and Ai Z and Niu B and Liu Z and Li T},
title = {Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.},
journal = {Science advances},
year = {2026},
doi = {10.1126/sciadv.aee5316},
note = {PMID: 42497271},
}
TY - JOUR AU - Zhou M AU - Li C AU - Kong R AU - Wang X AU - Yin Y AU - Wang D AU - Ai Z AU - Niu B AU - Liu Z AU - Li T TI - Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis. T2 - Science advances PY - 2026 DO - 10.1126/sciadv.aee5316 AN - PMID:42497271 ER -
The signaling mechanisms and developmental dynamics that govern the divergence of myocardial and epicardial lineages during human heart development remain poorly understood. Here, we developed a human pluripotent stem cell-based cardiac development model and employed time-course single-cell RNA sequencing to delineate cardiac lineage specification trajectories. We identified retinoic acid (RA) as a critical fate switch at the cardiac mesoderm stage. RA instructs epicardial lineage commitment of cardiac mesoderm through a primed-epicardium to proepicardium-like population and finally to epicardium, a process requiring precise BMP modulation. Conversely, RA absence directs cardiac mesoderm along a default myocardial pathway, yielding developing and mature cardiomyocytes. Both trajectories are governed by the hierarchical activation of key transcription factors. Our study integrates signaling and dynamics to elucidate the temporal regulatory network of the RA-BMP axis in human cardiac fate determination. These findings provide fundamental insights into human cardiogenesis and a crucial roadmap for modeling heart disease and advancing regenerative strategies.