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. Author manuscript; available in PMC: 2009 Mar 18.
Published in final edited form as: Nature. 2008 Aug 24;455(7211):401–405. doi: 10.1038/nature07213

Figure 3. Pluripotent Stem Cell-specific protein-protein interaction network detected by MATISSE.

Figure 3

Clusters from the sNMF k=12 analysis were used in combination with the transcriptional database to identify protein-protein interaction networks enhanced in PSC.

A. A large differentially expressed connected subnetwork (“PluriNet”) shows the dominance of cell cycle regulatory networks in PSC (see legend). All of the dark blue symbols are genes that are highly expressed in most PSCs compared to the other cell samples in the dataset. Front nodes as represented by Stem Cell Matrix expression data and back nodes as inferred by MATISSE are displayed with different colour shades.6 Highlighted in red are the interactions of a group of proteins associated with pluripotency in murine ePSC21. Interestingly, this subnetwork shows a significant enrichment in genes that are targeted in the genome by the transcription factors NANOG (p=5.88 * 10-4), SOX2 (p=0.058) and E2F (p=1.29 * 10-16, all p-values are Bonferroni corrected). For an interactive visualization of PluriNet, see www.stemcellmatrix.org.

B. Heat map-like visualization of PluriNet genes for samples from the test dataset: HUVEC (UC-EC, a-b, derived from three independent individuals), germ cell tumor derived pluripotent stem cells (tPSC-UN, d-f, lines GCT-C4, GCT-72, GCT-27X, derived from three independent individuals), induced pluripotent stem cells (iPSC-UN, g-i, BJ1-iPS12, MSC-iPS1, hFib2-iPS5 three independently derived lines from different somatic sources) and embryonic stem cells (ePSC-UN, j-l, lines Hues22, HSF6, ES2, derived from three independent blastocysts in three independent labs). Most PluriNet genes are markedly up-regulated in iPSC-UN and ePSC-UN. tPSC-UN do show a less consistent expression pattern. UC-EC show lower expression levels of most PluriNet genes. Please refer to Supplementary Figure 5 for a larger version of the same Net-Heatmaps

C. Analysis of genes from PluriNet in the context of phenotypes, which have been reported to result from specific genetic manipulations (e.g. gene knock-out) in mice in the MGI 3.6 phenotype ontology database (http://www.informatics.jax.org/). We find significant overrepresentation of phenotypes “lethality (perinatal/embryonic)”, “tumorigenesis”, “cellular”, “embryogenesis”, “reproductive system” and “life span and aging” among the genes in PluriNet. Although these broad categories might be rather unspecific surrogate markers for PSC function in mammals, this analysis might point towards PluriNet’s role in vivo. For more details, see also Supplementary Figure 6 and Supplementary Table 12.