The LARGE Principle in AFiPSCs Figure 6. Activation of a common ESC-like core transcriptional regulatory network in AFiPSCs and FiPSCs. (A) Venn diagram analysis comparing FiPSCs, ESCs and the parental fibroblast cell line HFF1 (Fibs). (B) Direct comparison of the ESC/AFiPSC (Figure 4C) and ESC/FiPSC (Figure 6A)-derived self-renewal signature gene lists. The overlap of 525 genes expressed in all analyzed pluripotent cells (AFiPSCs, FiPSCs, ESCs) represents the core self-renewal signature. (C) Of these 525 self-renewal-associated genes, those, bound by OCT4 or simultaneously by OCT4, SOX2 and NANOG as determined by ChIP-chip analyes [46,47], are depicted in the heatmap as LOG2 average expression signals. The heatmap is colored according to the color key on the bottom. Genes and samples were clustered by similar expression patterns using Eucledian distance measure. The table on the right identifies each gene to be bound by either OCT4 or by OCT4, SOX2 and NANOG (OSN) and shows expression changes upon siRNA- mediated OCT4 knockdown in ESC line H1, including the differential expression P-value (P-Val) [39]. doi:10.1371/journal.pone.0013703.g006 publications [15,29,30]. We have further demonstrated that AFiPSCs are, like ESCs, at an early developmental state, in which they are not only capable of forming derivatives of the three embryonic germ layers but also of the extraembryonic trophoblast lineage. This acquisition of key ESC characteristics during cellular reprogramming should be beneficial for the application of PLoS ONE | www.plosone.org 10 October 2010 | Volume 5 | Issue 10 | e13703