biostudies-literatureSong MNICHD NIH HHSNHLBI NIH HHSeabg0834https://www.ebi.ac.uk/biostudies/studies/S-EPMC8916722biostudies-literatureUnknown8(10)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 <i>gata5</i> at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic <i>gata5/6</i> 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 Science advancesGATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate.PMC8916722R01 HL108643R01 HD096770Christiaen LSong MLeslie MAleksandrova AWilson MDScott ICYuan XStutt NRacioppi CfalseGATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate.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 <i>gata5</i> at precardiac time points spanning zebrafish gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic <i>gata5/6</i> 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 2022-01-01T00:00:00Z2022 Mar2025-04-05T11:07:18.473Z2025-04-05T11:07:18.473ZS-EPMC89167223527572010.1126/sciadv.abg0834