Fig. 5

Differential gene expression analysis of density-dependent differentiation identifies molecules related to cellular adhesion and vascular genesis. a Gene expression analysis of embryonic stem cells (ESCs) as well as vascular progenitor cells (VPCs) seeded at density of 1,000 vs 10,000 cells/cm². The logarithmic fold change of cells seeded at 10,000 cells/cm² in comparison to 1,000 cells/cm² (LOG2(FC 10 K/1 K)) identifies density-depended processes. Gene symbols labeled with an asterisk * indicate significant differential expression with p-values below 0.05. Schematic model compares: b Poor differentiation efficiency of embryonic stem cells seeded at low density of 1,000 cells/cm², where isolated cells eventually die off. c Seeding of embryonic stem cells at high density of 10,000 cells/cm² results in expression of differentiation markers of vascular progenitor cells, which are a potent starting point for tissue engineering. d Enlarged diagram of cell-cell contact shows signaling processes and positive feedback enhancing differentiation: I. Cell-cell contacts mediate signals into nucleus. II. Transcriptional changes create positive feedback enforcing cell surface contacts and stimulating regulators of adherens junctions and desmosomes. III. Switch of metabolism from exponential, proliferative mode to differentiated phenotype. IV. Enforcement of new cell surface contacts. V. Propagation of differentiation state to neighboring cells