Lineage specification of Flk-1⁺ progenitors is associated with divergent Sox7 expression in cardiopoiesis

Embryonic stem cell differentiation recapitulates the diverse phenotypes of a developing embryo, traceable according to markers of lineage specification. At gastrulation, the vascular endothelial growth factor (VEGF) receptor, Flk-1 (KDR), identifies a mesoderm-restricted potential of embryonic stem cells. The multi-lineage propensity of Flk-1⁺ progenitors mandates the mapping of fate-modifying co-factors in order to stratify differentiating cytotypes and predict lineage competency. Here, Flk-1-based selection of early embryonic stem cell progeny separated a population depleted of pluripotent (Oct4, Sox2) and endoderm (Sox17) markers. The gene expression profile of the Flk-1⁺ population was notable for a significant upregulation in the vasculogenic Sox7 transcription factor, which overlapped with the emergence of primordial cardiac transcription factors GATA-4, Myocardin and Nkx2.5. Sorting the parental Flk-1⁺ pool with the chemokine receptor CXCR4 to enrich the cardiopoietic subpopulation uncovered divergent Sox7 expression, with a 7-fold induction in non-cardiac compared to cardiac progenitors. Bioinformatic resolution sequestered a framework of gene expression relationship between Sox transcription factor family members and the Flk-1/CXCR4 axes with significant integration of β-catenin signaling. Thus, differential Sox7 gene expression presents a novel biomarker profile, and possible regulatory switch, to distinguish cardiovascular pedigrees within Flk-1⁺ multi-lineage progenitors.