GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate

作者：Mengyi Song, Xuefei Yuan, Claudia Racioppi, Meaghan Leslie, Nathan Stutt, Anastasiia Aleksandrova, Lionel Christiaen, Michael D. Wilson, Ian C. Scott · 发表于：Science Advances · 年份：2022 · DOI：10.1126/sciadv.abg0834 · 被引用次数：47 · 研究领域：Congenital heart defects research、Congenital Heart Disease Studies、Tracheal and airway disorders

GATA4/5/6 transcription factors play essential, conserved roles in heart development. To understand how GATA4/5/6 modulates the mesoderm-to-cardiac fate transition, we labeled, isolated, and performed single-cell gene expression analysis on cells that express gata5 at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic gata5/6 expression. In the absence of Gata5/6, the population structure of mesendoderm-derived cells was substantially altered. In addition to the expected absence of cardiac mesoderm, we confirmed a concomitant expansion of cranial-pharyngeal mesoderm. Moreover, Gata5/6 loss led to extensive changes in chromatin accessibility near cardiac and pharyngeal genes. Functional analyses in zebrafish and the tunicate Ciona , which has a single GATA4/5/6 homolog, revealed that GATA4/5/6 acts upstream of tbx1 to exert essential and cell-autonomous roles in promoting cardiac and inhibiting pharyngeal mesoderm identity. Overall, cardiac and pharyngeal mesoderm fate choices are achieved through an evolutionarily conserved GATA4/5/6 regulatory network.