Figure 1.
Major features and assumptions of the SCSC method.
1. G1–G8 are eight genes in Species 1, which have orthologues G1′–G8′ in Species 2. 2. G4 and G9′ do not have orthologues, but they participate in the clustering analysis. 3. The shapes of the lines represent gene expression patterns. For example, G1 has an increasing pattern and G6′ has a first decreasing and then increasing pattern. 4. The genes with the same color, except for the black color, are clustered together. Genes in black are “scattered” genes, which form a singleton cluster each.
Figure 2.
SCSC clusters of mES and hES cell differentiation data.
Representative transcription regulators are listed in each cluster. Thick lines enclose clusters with upregulation in either mouse or human ES cells. Dotted lines enclose the conserved clusters with upregulation in ES cells of both species. Detailed expression patterns of every cluster and sample information are given in Figure S2.
Figure 3.
Induced components of signaling pathways in hES and mES cells.
The gene induced in either hES or mES cells, i.e., Clusters (2, *), (3, *) and (*, 3), are mapped onto all the signaling pathways documented in the KEGG database [33] and plotted using Cytoscape software (www.cytoscape.org). Gray, blue and green nodes represent genes that are induced in hES cells only, mES cells only or both (conserved), respectively. The edges between any two nodes represent known protein-protein interactions documented in Cytoscape.
Figure 4.
Rewiring of the KLF regulatory module.
Nodes represent upregulated genes in ES cells in a conserved (blue, upregulated in both hES and mES cells) or species-specific (red, upregulated in mES cells only) manner. Edges represent positive regulatory relationships (activation) that are validated by ChIP-chip and RNAi data in both species (dark blue), in mouse only (red), or in human only (light blue). As the KLF module appears to have lost its regulatory function in hES cells, its target genes ESRRB, FOXD3 and SOCS3 have consistently lost their upregulation in hES cells as well (A). However, LIN28 and NODAL, which are upregulated by the KLF module in mES cells, remain upregulated in hES cells. Their upregulation in hES cells might be activated by NANOG and OCT4 instead (B).
Table 1.
Distribution of genes participating in six signaling pathways in the ES clusters.