The naive state of human pluripotent stem cells: a synthesis of stem cell and preimplantation embryo transcriptome analyses - PubMed (original) (raw)

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The naive state of human pluripotent stem cells: a synthesis of stem cell and preimplantation embryo transcriptome analyses

Kevin Huang et al. Cell Stem Cell. 2014.

Abstract

Here we use a systems biology approach to comprehensively assess the conservation of gene networks in naive pluripotent stem cells (PSCs) with preimplantation embryos. While gene networks in murine naive and primed pluripotent states are reproducible across data sets, different sources of human stem cells display high degrees of variation, partly reflecting disparities in culture conditions. Finally, naive gene networks between human and mouse PSCs are not well conserved and better resemble their respective blastocysts.

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Figures

Figure 1

Figure 1. Transcription Networks in Preimplantation Embryos and Naive/Primed Pluripotent States

(A) Heatmap showing the significance of gene overlaps between mouse 2i/LIF, serum/LIF, and primed modules (x axis) and stage-specific mouse preimplantation embryo modules (y axis). Mouse stem cell modules were defined by identifying clusters of correlated transcripts to 2i/LIF, serum/LIF, and primed state asshown in Figure S1. Each cell contains the average p value (geometric mean) from gene intersects of 2i/LIF, serum, and primed modules with two separate mouse preimplantation data sets (Tang et al., 2011; Xie et al., 2010). Color legend represents –log10 p value based on the hypergeometric test. (B) Heatmap of module preservation scores between mouse preimplantation stages and mPSCs. Module preservation scores are represented by the median Zsummary statistic from three independent mouse preimplantation data sets to ensure sufficient coverage of all preimplantation stages (Tang et al., 2011; Xie et al., 2010; Xue et al., 2013). Shown is the preservation level of stage-specific preimplantation reference modules (y axis) within the mPSC data sets. Generally, a Zsummary score of less than 2 indicates that the reference module is not preserved in the test data set, Zsummary of 5 is moderately preserved, and a Zsummary score above 10 is strongly preserved. Note: epiblast cells (y axis) are single-cell transcriptome data from E4.5 embryos (Tang et al., 2011), and EpiSCs (x axis) are stabilized culture derived from E5.75 embryos (Table S1A).

Figure 2

Figure 2. Transcription Networks in Preimplantation Embryos and Naive/Primed Pluripotent States

(A) Heatmap containing the significance levels of gene intersects between 2i/LIF, serum/LIF, and primed modules (y axis) with naive and primed hESCs from six different methods (x axis). Each cell contains the number of intersecting genes and the p value of the intersection. (B) Heatmap showing the significance of gene overlaps between human preimplantation embryos and six different methods for producing naive hESCs. The x axis shows naive and primed hESC modules from different groups and the y axis shows stage-specific modules of human preimplantation development. Comparison with consensus naive and primed modules (as defined in Figure S2B) is also shown. Each cell contains the average p value (geometric mean) from gene intersects of naive and primed modules with three separate human preimplantation data sets (Vassena et al., 2011; Xie et al., 2010; Yan et al., 2013). Color legend represents –log10 p value based on the hypergeometric test. (C) Heatmap of human preimplantation module preservation across multiple naive hESC data sets. Module preservation scores are represented by the median Zsummary statistic from three independent human preimplantation data sets (Vassena et al., 2011; Xie et al., 2010; Yan et al., 2013). Preservation levels of pre-implantation stage-specific modules (y axis) across multiple naive/primed hESCs data sets are shown.

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