STRA6 is essential for induction of vascular smooth muscle lineages in human embryonic cardiac outflow tract development.

Dysregulation of the RA signaling can cause cardiac OFT defects, however, the detailed mechanisms by which STRA6 mutations lead to cardiac malformations have remained unclear. Our study highlights a critical role of human-specific STRA6 progenitors for proper induction of vascular SMCs that is essential for normal OFT formation. These results shed light on novel and human-specific CHD programs, driven by STRA6 mutations. Thus, our study paves the way for further studies of deciphering the origins and the disease mechanisms of a rare genetic disorder Matthew-Wood syndrome, which would help us develop diagnosis, prevention, and novel treatment for the disease.