Figure 1

Phenotypic changes and transcriptome dynamism during cardiac stem cell differentiation. (a) Electron microscopy visualized morphological changes occurring during guided stem cell cardiogenesis (left column) with associated expression and distribution of the selected cardiac transcription factor MEF2C and the cardiac contractile protein α-actinin (right column). Cell stage is given in the top left corner of each panel with associated scale bars at the bottom right. First column: ES-LIF(+), 2.5 μm; ES-LIF(-), 5 μm; cardiopoietic cell (CP), 25 μm; cardiomyocyte (CM), 5 μm. All scale bars in the second column indicate 10 μm. Nuclei were counterstained with DAPI. (b) Transcriptional profiling of samples from each stage of stem cell-derived cardiomyocyte formation. Changes in gene expression were plotted on a semi-log scale graph using normalized intensity values as a function of the stage of differentiation. The color scale indicates increased expression (red), no change (yellow) and decreased expression (blue). Associated numbers indicate fold change, where red and blue indicate a respective minimum five-fold up- or downregulation in expression value. (c) Hierarchical clustering of changing genes during differentiation. The condition tree on right illustrates similarity of replicates within each stage. Numbers above branches are the calculated Euclidean distances between the two samples at the left termini. Smaller numbers indicate less dissimilarity between samples while higher numbers indicate an increase in dissimilarity. The shaded box identifies emergence of cardiac specficity (orange, CP) with transition to stem cell derived cardiomyocyte (cyan, CM). The color scale indicates relative changes in gene expression as described previously.