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Chunk #5 — Results — Cell Type of Origin Contributes Minimally to iPSC Variability

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Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential.
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To eliminate variability resulting from genetic background, we compared F- versus B-iPSCs for each donor. Using a local-pooled-error (LPE) test, a statistical test well suited for small sample sizes (Jain et al., 2003), we identified 24 (T14B- versus F-iPSCs), 13 (T42B- versus F-iPSCs), 6 (T53B- versus F-iPSCs), and 158 (T55B- versus F-iPSCs) differentially expressed genes between the isogenic iPSC lines (Figure 1D and Table S1). Of interest, we noticed that T42- and T55-derived iPSCs showed larger intra-line variability compared with T14- and T53-derived iPSC lines (Figure S2C). MEG3 was the only common element for all four donors. In addition, TCERG1L, COL3A1, and HAND1 were common between three donors (T14, T42, and T55) (Figure S2D). These data are in line with previous studies showing that the imprinted genes MEG3 and TCERG1L are frequently differentially expressed between PSC lines (Lister et al., 2011, Stadtfeld et al., 2010, Wang et al., 2013). To increase the power of analysis we again used the arbitrary FC cutoff >1 and identified 134–435 differentially expressed genes between isogenic iPSC lines (Table S2). After examination of gene ontology