Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency

We reported RNA-seq transcriptome profiling of WT and Cripto KO ESC→EpiSC transition using the Illumina HiSeq platform. Whole-genome expression revealed that epiblast associated-genes were all severely reduced in absence of Cripto compare to WT. Interestingly, besides a set of common genes deregulated in both WT and Cripto KO ESC→EpiSC transition, we identified two different sets of genes that were uniquely deregulated. We find a large cluster of genes coding for components of the five respiratory electron transport complexes, which are involved in mitochondrial oxidative phosphorylation, downregulated only in WT ESC→EpiSC transition, while their expression was unvaried in Cripto KO. Moreover the RNAseq analysis reveals a set of genes that were uniquely upregulated in Cripto KO, such as Hox genes and trophoectodermal markers. RNAseq data and validation both at RNA and protein level provide new evidences that Cripto is required for the metabolic reprogramming that occurs in the conversion of mouse ESCs into EpiSCs, preserving ESC lineage restriction.