Figure 5

Transcription factors within the MSC expression footprint. (A) Table of 11 meta-regulators found to be enriched on the TFBS of 135 TFs detected in the MSC expression footprint. (B) DNA methylation distributions –densities versus Beta values– corresponding to 135 expressed MSC-TFs (red) and to other sets of 135 randomly selected TFs (black). The plot shows higher accumulation of methylation measurements around lower values of Beta for MSC-TFs. (C) Table of expression values of log2 (FPKM _sum ) corresponding to five TFs related to pluripotency (KLF4, c-MYC, POU5F1, SOX2 and NANOG); and RNA-Seq raw profiles of KLF4 and MYC genes in BM- and PL-MSC samples. (D) DNA methylation distributions –Beta values– corresponding to the CpGs associated to 4 TFs. Wilcoxon tests proving significant differences in these analyses gave the following p-values: KLF4 vs POU5F1, p-value = 2.40×10e^-4; KLF4 vs SOX2, p-value = 2.63×10e^-2; MYC vs POU5F1, p-value = 1.89×10e^-6; MYC vs SOX2, p-value = 0.782×10e^-6 (all parameters of the statistical tests presented in this figure are included in Additional file 12: Table S8) (E) Protein interaction network including the MSC-TFs found. Edge-thickness (blue lines) and number represents the number of experimental evidences that support a given protein-protein interaction (PPI). Shaded groups represent structural families. The 17 TFs that were found to regulate the MSCs gene expression footprint are labeled with red names and enclosed by a square (instead of a circle like the rest of the nodes). Within these 17 TFs, the nodes corresponding to the 11 TF meta-regulators (detailed in 5A) are also labeled with red names but larger squares. Nodes with border in blue (11 genes) are not linked in the network, but they are structural paralogs of some of the linked nodes placed aside.