Sox7 regulates lineage decisions in cardiovascular progenitor cells

Specification of the mesodermal lineages requires a complex set of morphogenetic events orchestrated by interconnected signaling pathways and gene regulatory networks. The transcription factor Sox7 has critical functions in differentiation of multiple mesodermal lineages, including cardiac, endothelial, and hematopoietic. Using a doxycycline-inducible mouse embryonic stem cell (mESC) line, we have previously shown that expression of Sox7 in cardiovascular progenitor cells promotes expansion of endothelial progenitor cells. Here, we show that the ability of Sox7 to promote endothelial cell fate occurs at the expense of the cardiac lineage. Using ChIP-Seq coupled with ATAC-Seq we identify downstream target genes of Sox7 in cardiovascular progenitor cells and, by integrating these data with transcriptomic analyses, we define Sox7-dependent gene programs specific to cardiac and endothelial progenitor cells. Further, we demonstrate a protein-protein interaction between SOX7 and GATA4 and provide evidence that Sox7 interferes with the transcriptional activity of Gata4 on cardiac genes. In addition, we show Sox7 modulates WNT and BMP signaling during cardiovascular differentiation. Our data represent the first genome-wide analysis of Sox7 function and reveal a critical role for Sox7 in regulating signaling pathways that affect cardiovascular progenitor cell differentiation. Sox7 function during mesoderm specification was investigated using doxycycline-inducible embryonic stem (ES) cells. ATAC-seq was used to identify changes in chromatin accessibility induced by Sox7 upon 1-day induction in cardiac (CPC) and endothelial (EPC) progenitors. ChIP-seq was used to determine Sox7 genomic occupancy in mouse ES cells undergoing specification (1-day and non-induced). Gene expression changes induced by Sox7 in mouse differentiating ES cells (12-hrs and non-induced) were assessed by RNA-seq. All data was collected from day 4 EBs.