In-depth Parallel Meta-analysis of Cells Undergoing Reprogramming into Pluripotency and Trophectoderm States

During early embryogenesis, totipotent cells undergo asymmetric cell divisions, resulting in two compartments in the early embryo: the inner cell mass (ICM) that gives rise to the embryo proper and Trophectoderm (TE) that forms extraembryonic tissues such as the placenta. It is only at the 32-64- cell stage when a clear segregation between the two cell types can be observed. This proposes a ‘T’-like model where cells of the early embryo undergo a relatively similar changes in their transcriptome and epigenome before specification (2-32-cell stage). Here, we sought to understand whether cells acquiring pluripotency and trophectoderm, by reprogramming factors, share similar processes between themselves such as those of the early embryo. To that end, we conducted a parallel meta-analysis on cells undergoing reprogramming into induced pluripotent stem cells (iPSCs) and induced trophoblast stem cells (iTSCs) and compared their transcriptome, epigenome and chromatin architecture along the process. Our analysis revealed that, in contrast to cells of the pre-segregation embryo that resemble each other in each stage, cells undergoing reprogramming to pluripotency and trophectoderm, exhibit a unique and specific trajectory from the beginning of the process till the end. Although similar processes such as somatic identity loss, proliferation, MET and metabolic shift occur in the two models, each of the processes uses a completely different set of genes and regulatory elements to induce its own state. This parallel meta-analysis may serve as a powerful tool to understand nuclear reprogramming and cell fate.