Global gene and small RNA sequencing analysis of reprogrammed cells.

<p>(A–B) Genes and small RNAs significantly upregulated more than 2-fold over control (red), significantly downregulated more than 2-fold below control (green), and genes without significant changes of 2-fold or more (blue) are plotted logarithmically for 6TF versus vehicle control. Well-known liver and liver-repair associated genes are upregulated (labeled in red), whereas fibroblast associated genes are downregulated (labeled in green). Pluripotency genes and control genes are unchanged (labeled in blue). Well-known hepatic miRNAs, such as miR-122, are upregulated (labeled in red). False discovery rates less than 0.001 for genes and p-values less than 0.05 for small RNAs were deemed significant. (C) Of the top 25 most upregulated genes in reprogrammed cells, twelve (nearly half) are associated with liver or liver-repair (red), four are associated with other endodermal tissues (blue), and four are histones (green). Histone genes were also globally upregulated in reprogrammed cells (D); mean and 75% and 25% quantiles are indicated. The full expression data for all genes (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100134#pone.0100134.s010" target="_blank">Tables S4</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100134#pone.0100134.s011" target="_blank">S5</a>, and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100134#pone.0100134.s012" target="_blank">S6</a>) and small RNAs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100134#pone.0100134.s013" target="_blank">Tables S7</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100134#pone.0100134.s014" target="_blank">S8</a>, and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100134#pone.0100134.s015" target="_blank">S9</a>) are provided in the supporting information.