A Mesoderm-Derived Precursor for Mesenchymal Stem and Endothelial Cells

SummaryAmong the three embryonic germ layers, the mesoderm is a major source of the mesenchymal precursors giving rise to skeletal and connective tissues, but these precursors have not previously been identified and characterized. Using human embryonic stem cells directed toward mesendodermal differentiation, we show that mesenchymal stem/stromal cells (MSCs) originate from a population of mesodermal cells identified by expression of apelin receptor. In semisolid medium, these precursors form FGF2-dependent compact spheroid colonies containing mesenchymal cells with a transcriptional profile representative of mesoderm-derived embryonic mesenchyme. When transferred to adherent cultures, individual colonies give rise to MSC lines with chondro-, osteo-, and adipogenic differentiation potentials. Although the MSC lines lacked endothelial potential, endothelial cells could be derived from the mesenchymal colonies, suggesting that, similar to hematopoietic cells, MSCs arise from precursors with angiogenic potential. Together, these studies identified a common precursor of mesenchymal and endothelial cells, mesenchymoangioblast, as the source of mesoderm-derived MSCs.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (163 K)Download as PowerPoint slideHighlights► Mesodermal MSCs develop from an angiogenic precursor named mesenchymoangioblast ► The mesenchymoangioblast can be identified using a colony-forming assay ► Apelin receptor (APLNR) marks mesodermal precursors during hESC differentiation ► Mesenchymo- and hemangioblasts arise sequentially from APLNR+ mesodermal cells