Transcriptional landscape changes during human embryonic stem cell derivation

Currently, there is only minimal information elucidating the transcriptional changes occurring during the in vitro transition of the inner cell mass (ICM) towards the human embryonic stem cell (hESC) stage and the role played by the post inner cell mass intermediate (PICMI). In this study, we perform in-depth analysis of the transcriptional heterogeneity between these three stages of hESC derivation in order to correlate their downstream effects on pluripotency states and differentiation. We reveal that although PICMI is transcriptionally in close proximity to the hESC profile and distinct from ICM, it exhibits upregulation of primordial germ cell markers, dependence on LIF signaling, upregulation of naïve pluripotency-specific signaling networks and appears to be a switching point from naïve to primed pluripotency. This indicates similarities with mouse epiblast-like cells displaying a transient state of pluripotency, between naïve and primed pluripotent states. Overall, we highlight the need to gain insight into the molecular and transcriptional landscape during hESC derivation, which will further help in the derivation of human PGCs and naïve hESCs in vitro which remains inefficient.