Partially reprogrammed stem cell modules in GF-activated CB myeloid progenitors are rapidly reconfigured to hESC-like patterns.

<p>(<b>a</b>) Illumina microarray expressions of ESC-like gene modules (MYC, PRC1, PRC2, and Core; see <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042838#pone.0042838.s012" target="_blank">Table S1</a></b> for gene lists). Shown are donor cell populations with (+) and without (−) 4F episomal nucleofections, and with (+) and without (−) BMSC-priming: adult fibroblasts (F), Day -3 unstimulated CB cells (D-3 CB), Day 0 FTK GF-stimulated CB cells (D0), Day 3+/− BMSC-primed (D3), and bulk Day 23 early CB-iPSC culture (D23 iPSC). These early D23 iPSC populations were already composed of >50–60% populations with fully-reprogrammed TRA-1-81⁺NANOG⁺ phenotypes. Undifferentiated H9 hESC samples served as control (hESC). Module expressions represent log2 mean-subtracted normalized values of signal intensities from averaged, independent biological replicate microarray samples (n = 3 per condition). Although they possessed a transcriptionally inactive Core module, day 0 GF-activated CB progenitors expressed active ESC and MYC modules, and inactive PRC1, and PRC2 modules at mean expression levels that were already comparable to levels in hESC. The annotation and references of all genes in each module is provided in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042838#pone.0042838.s012" target="_blank">Table S1</a></b>. (<b>b</b>) Partially reprogrammed ESC module <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042838#pone.0042838-Wong1" target="_blank">[26]</a> expression in CB progenitors. Legend for each sample is the same as above. Unsupervised hierarchical clustering heatmaps of (<b>b</b>) expression and (<b>c</b>) Box plots of log2 mean-normalized values of the ESC module gene signal intensities in somatic target populations, hESC, and reprogrammed cell lines. The heatmap’s color scale was chosen to emphasize subtle mid-range change. The resulting values emphasize relative expression across cell types rather than relative absolute expression across genes. This box and whisker plots (right panels) depict the log2 mean-subtracted normalized values of signal intensities of genes comprising the module set for each cell type indicated from Illumina array data. The top and bottom of a box mark the 75^th and 25^th percentile log2 signal values, respectively, while the bar at the middle denotes the median. The whiskers above and below each box mark the upper 90^th and lower 10^th percentiles. Paired tests with significance <i>p</i><0.05 (*) or without significance (<i>NS</i>; p>0.05) with values of control hESC are indicated.