Figure 7. Activated Lipid Biosynthesis Is a Shared Signature of E8 hPSCs and the Human Pre-EPI.
(A) Unsupervised hierarchical clustering of lipid-related DEGs (143 genes) in 4 of 5 naive versus primed studies (E8 versus KSR; Boroviak et al., 2015; Marks et al., 2012; Takashima et al., 2014; Yan et al., 2013).
(B) Unsupervised hierarchical clustering of signaling-related DEGs (214 genes) in 4 of the 5 naive versus primed studies (E8 versus KSR).
(C) Correlation plot of GO/KEGG pathway regulation in E8 versus KSR (y axis) and in human pre-EPI versus hESCs (x axis) (Yan et al., 2013). Each dot represents the average t-score of pathway enrichment for each GO term or KEGG pathway. Colored dots are pathways associated with lipid metabolism or cell signaling.
(D) Model of in vitro and in vivo regulation of human pluripotency through exogenous lipids. Low exogenous lipids (yellow) during pre-implantation lead to depletion of zygote-derived storage (purple), promoting de novo lipogenesis (blue). Low intracellular lipids endogenously inhibit ERK signaling, instructing naïve features (green). A lipid-rich post-implantation environment through maternal exchange (yellow) leads to intracellular lipid accumulation (purple) and ERK activation, suppressing de novo lipogenesis and promoting primed features (red).